Substituted N-Aliphatic-N-Aromatictertiary-Heteroalkylamines useful for inhibiting cholesteryl ester transfer protein activity

ABSTRACT

The invention relates to substituted N-Aliphatic-N-Aromatic tertiary - Heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis, dyslipidemia, and other coronary artery disease.

FIELD OF THE INVENTION

[0001] This invention is in the field of treating cardiovascular disease, and specifically relates to compounds, compositions and methods for treating atherosclerosis and other coronary artery disease. More particularly, the invention relates to substituted N-Aliphatic-N-Aromatictertiary-Heteroalkylamine compounds that inhibit cholesteryl ester transfer protein (CETP), also known as plasma lipid transfer protein-1.

BACKGROUND OF THE INVENTION

[0002] Numerous studies have demonstrated that a low plasma concentration of high density lipoprotein (HDL) cholesterol is a powerful risk factor for the development of atherosclerosis (Barter and Rye, Atherosclerosis, 121, 1-12 (1996)). HDL is one of the major classes of lipoproteins that function in the transport of lipids through the blood. The major lipids found associated with HDL include cholesterol, cholesteryl ester, triglycerides, phospholipids and fatty acids. The other classes of lipoproteins found in the blood are low density lipoprotein (LDL) and very low density lipoprotein (VLDL). Since low levels of HDL cholesterol increase the risk of atherosclerosis, methods for elevating plasma HDL cholesterol would be therapeutically beneficial for the treatment of atherosclerosis and other diseases associated with accumulation of lipid in the blood vessels. These diseases include, but are not limited to, coronary heart disease, peripheral vascular disease, and stroke.

[0003] Atherosclerosis underlies most coronary artery disease (CAD), a major cause of morbidity and mortality in modem society. High LDL cholesterol (above 180 mg/dl) and low HDL cholesterol (below 35 mg/dl) have been shown to be important contributors to the development of atherosclerosis. Other diseases, such as peripheral vascular disease, stroke, and hypercholesterolaemia are negatively affected by adverse HDL/LDL ratios. Inhibition of CETP by the subject compounds is shown to effectively modify plasma HDL/LDL ratios, and to check the progress and/or formation of these diseases.

[0004] CETP is a plasma protein that facilitates the movement of cholesteryl esters and triglycerides between the various lipoproteins in the blood (Tall, J. Lipid Res., 34, 1255-74 (1993)). The movement of cholesteryl ester from HDL to LDL by CETP has the effect of lowering HDL cholesterol. It therefore follows that inhibition of CETP should lead to elevation of plasma HDL cholesterol and lowering of plasma LDL cholesterol, thereby providing a therapeutically beneficial plasma lipid profile (McCarthy, Medicinal Res. Revs., 13, 139-59 (1993); Sitori, Pharmac. Ther., 67,443-47 (1995)). This exact phenomenon was first demonstrated by Swenson et al., (J. Biol. Chem., 264, 14318 (1989)) with the use of a monoclonal antibody that specifically inhibited CETP. In rabbits, the antibody caused an elevation of the plasma HDL cholesterol and a decrease in LDL cholesterol. Son et al. (Biochim. Biophys. Acta 795, 743-480 (1984)), Morton et al. (J. Lipid Res. 35, 836-847 (1994)) and Tollefson et al. (Am. J. Physiol., 255, (Endocrinol. Metab. 18, E894-E902 (1988))) describe proteins from human plasma that inhibit CETP. U.S. Pat. No. 5,519,001, issued to Kushwaha et al., describes a 36 amino acid peptide derived from baboon apo C-1 that inhibits CETP activity. Cho et al. (Biochim. Biophys. Acta 1391, 133-144 (1998)) describe a peptide from hog plasma that inhibits human CETP. Bonin et al. (J. Peptide Res., 51, 216-225 (1998)) disclose a decapeptide inhibitor of CETP. A depsipeptide fungal metabolite is disclosed as a CETP inhibitor by Hedge et al. in Bioorg. Med. Chem. Lett., 8, 1277-80 (1998).

[0005] There have been several reports of non-peptidic compounds that act as CETP inhibitors. Barrett et al. (J. Am. Chem. Soc., 188, 7863-63 (1996)) and Kuo et al. (J. Am. Chem. Soc., 117, 10629-34 (1995)) describe cyclopropane-containing CETP inhibitors. Pietzonka et al. (Bioorg. Med. Chem. Lett, 6, 1951-54 (1996)) describe phosphonate-containing analogs of cholesteryl ester as CETP inhibitors. Coval et al. (Bioorg. Med. Chem. Lett., 5, 605-610 (1995)) describe Wiedendiol-A and -B, and related sesquiterpene compounds as CETP inhibitors. Japanese Patent Application No. 10287662-A describes polycyclic, non-amine containing, polyhydroxylic natural compounds possessing CETP inhibition properties. Lee et al. (J. Antibiotics, 49, 693-96 (1996)) describe CETP inhibitors derived from an insect fungus. Busch et al. (Lipids, 25, 216220, (1990)) describe cholesteryl acetyl bromide as a CETP inhibitor. Morton and Zilversmit (J. Lipid Res., 35, 836-47 (1982)) describe that p-chloromercuriphenyl sulfonate, p-hydroxymercuribenzoate and ethyl mercurithiosalicylate inhibit CETP. Connolly et al. (Biochem. Biophys. Res. Comm. 223, 42-47 (1996)) describe other cysteine modification reagents as CETP inhibitors. Xia et al. describe 1,3,5-triazines as CETP inhibitors (Bioorg. Med. Chem. Lett., 6,919-22 (1996)). Bisgaier et al. (Lipids, 29, 811-8 (1994)) describe 4-phenyl-5-tridecyl4H-1,2,4-triazole-thiol as a CETP inhibitor. Oomura et al. disclose non-peptidic tetracyclic and hexacyclic phenols as CETP inhibitors in Japanese Patent Application No. 10287662. In WO Patent Application No. 09914204, Sikorski describes 1,2,4-triazolylthiols useful as chlolesteryl ester transfer protein inhibitors.

[0006] Some substituted heteroalkylamine compounds are known. In European Patent Application No. 796846, Schmidt et al. describe 2-aryl-substituted pyridines as cholesteryl ester transfer protein inhibitors useful as cardiovascular agents. One substitutent at C3 of the pyridine ring can be an hydroxyalkyl group. In European Patent Application No. 801060, Dow and Wright describe heterocyclic derivatives substituted with an aldehyde addition product of an alkylamine to afford 1-hydroxy-1-amines. These are reported to be β3-adrenergic receptor agonists useful for treating diabetes and other disorders. In Great Britain Patent Application No. 2305665, Fisher et al. disclose 3-agonist secondary amino alcohol substituted pyridine derivatives useful for treating several disorders including cholesterol levels and artherosclerotic diseases. In European Patent Application No. 818448, Schmidt et al. describe tetrahydroquinoline derivatives as chlolesteryl ester transfer protein inhibitors. European Patent Application No. 818197, Schmek et al. describe pyridines with fused heterocycles as cholesteryl ester transfer protein inhibitors. Brandes et al. in German Patent Application No. 19627430 describe bicyclic condensed pyridine derivatives as cholesteryl ester transfer protein inhibitors. In WO Patent Application No. 09839299, Muller-Gliemann et al. describe quinoline derivatives as cholesteryl ester transfer protein inhibitors. U.S. Pat. No. 2,700,686, issued to Dickey and Towne, describes N-(2-haloalkyl-2-hydroxyethyl)amines in which the amine is further substituted with either 1 to 2 aliphatic groups or one aromatic group and one aliphatic group. U.S. Pat. No. 2,700,686 further describes a process to prepare the N-(2-haloalkyl-2-hydroxyethyl)amines by reacting halogenated-1,2-epoxyalkanes with the corresponding aliphatic amines and N-alkylanilines and their use as dye intermediates.

SUMMARY OF THE INVENTION

[0007] The present invention provides a class of compounds that can be used to inhibit cholesteryl ester transfer protein (CETP) activity and that have the general structure:

[0008] In another aspect, the present invention includes pharmaceutical compositions comprising a pharmaceutically effective amount of the compounds of this invention and a pharmaceutically acceptable carrier.

[0009] In another aspect, this invention relates to methods of using these inhibitors as therapeutic agents in humans to inhibit cholesteryl ester transfer protein (CETP) activity, thereby decreasing the concentrations of low density lipoprotein (LDL) and raising the level of high density lipoprotein (HDL), resulting in a therapeutically beneficial plasma lipid profile. The compounds and methods of this invention can also be used to treat dyslipidemia (hypoalphalipoproteinemia), hyperlipoproteinaemia (chylomicronemia and hyperapobetalipoproteinemia), peripheral vascular disease, hypercholesterolaemia, atherosclerosis, coronary artery disease and other CETP-mediated disorders. The compounds can also be used in prophylactic treatment of subjects who are at risk of developing such disorders. The compounds can be used to lower the risk of atherosclerosis. The compounds of this invention would be also useful in prevention of cerebral vascular accident (CVA) or stroke. Besides being useful for human treatment, these compounds are also useful for veterinary treatment of companion animals, exotic animals and farm animals such as primates, rabbits, pigs, horses, and the like.

DESCRIPTION OF THE INVENTION

[0010] The present invention relates to a class of compounds comprising substituted N-Aliphatic-N-Aromatictertiary-Heteroalkylamines which are beneficial in the therapeutic and prophylactic treatment of coronary artery disease as given in Formula I-WA (also referred to herein as “alicyclic/cyclic aryl/heteroaryl heteroalkylamines”):

[0011] or a pharmaceutically-acceptable salt thereof, wherein;

[0012] n is an integer selected from 1 through 4;

[0013] A and Q are independently selected from the group consisting of —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H,

[0014] with the provisos that one of A and Q must be AQ-1 and that one of A and Q must be selected from the group consisting of AQ-2 and —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H;

[0015] T is selected from the group consisting of a single covalent bond, O, S, S(O), S(O)_(2,) C(R₃₃)═C(R₃₅), and C≡C;

[0016] v is an integer selected from 0 through 1 with the proviso that v is 1 when any one of R₃₃, R₃₄, R₃₅, and R₃₆ is aryl or heteroaryl;

[0017] u and w are integers independently selected from 0 through 6;

[0018] A₁ is C(R₃₀);

[0019] D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ is a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ is O, no more than one of D₁, D₂, J₁ J₂ and K₁ is S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ are N;

[0020] B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C, C(R₃₀), N, O, S and a covalent bond with the provisos that no more than 5 of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are a covalent bond, no more than two of B_(1,) B₂, D₃, D₄, J₃, J₄ and K₂ are O, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are S, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are simultaneously O and S, and no more than two of B₁, B₂, D₃, D₄, J₃, J₄and K₂ are N;

[0021] B₁ and D₃, D₃ and J₃, J₃ and K₂, K₂ and J₄, J₄ and D₄, and D₄ and B₂ are independently selected to form an in-ring spacer pair wherein said spacer pair is selected from the group consisting of C(R₃₃)═C(R₃₅) and N═N with the provisos that AQ-2 must be a ring of at least five contiguous members, that no more than two of the group of said spacer pairs are simultaneously C(R₃₃)═C(R₃₅), and that no more than one of the group of said spacer pairs can N═N unless the other spacer pairs is other than C(R₃₃)═C(R₃₅), O, N, and S;

[0022] R₁₆ is selected from the group consisting of hydrido, alkyl, acyl, aroyl, heteroaroyl, and trialkylsilyl;

[0023] X is selected from the group consisting of O, H, F, S, S(O), NH, N(OH), N(alkyl), and N(alkoxy) with the proviso that there is no R₁₆ wherein X is H or F;

[0024] R₁ is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl, and haloalkenyloxyalkyl;

[0025] R₂ is selected from the group consisting of hydrido, aryl, aralkyl, alkyl, alkenyl, alkenyloxyalkyl, haloalkyl, haloalkenyl, halocycloalkyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, dicyanoalkyl, and carboalkoxycyanoalkyl;

[0026] R₃ is selected from the group consisting of hydrido, hydroxy, cyano, aryl, aralkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, heteroaryl, alkenyloxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0027] Y is selected from a group consisting of a covalent single bond, (C(R₁₄)₂)_(q) wherein q is an integer selected from 1 through 4 and (CH(R₁₄))_(g)—O—(CH(R₁₄))_(p) wherein g and p are integers independently selected from 0 through 2;

[0028] R₁₄ is selected from the group consisting of hydrido, hydroxy, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, carboxamidoalkyl;

[0029] Z is selected from the group consisting of covalent single bond, (C(R₁₅)₂)_(q) wherein q is an integer selected from 1 through 2, and (CH(R₁₅))_(j)—O—(CH(R₁₅))_(k) wherein j and k are integers independently selected from 0 through 2;

[0030] R₁₅ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

[0031] R₃₀ is selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl with the proviso that R₃₀ is selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

[0032] R₃₀, when bonded to A₁, is taken together to form an intra-ring linear spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the point of bonding of a group selected from the group consisting of R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ wherein said intra-ring linear spacer is selected from the group consisting of a covalent single bond and a spacer moiety having from 1 through 6 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 10 contiguous members, a cycloalkenyl having from 5 through 10 contiguous members, and a heterocyclyl having from 5 through 10 contiguous members;

[0033] R₃₀, when bonded to A₁, is taken together to form an intra-ring branched spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the points of bonding of each member of any one of substituent pairs selected from the group consisting of subsitituent pairs R₁₀ and R₁₁, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₀ and R₁₂, R₁₁ and R₃₁, R₁₁, and R₃₂, R₁₁, and R₁₂, R₃₁ and R₃₂, R₃₁ and R₁₂, and R₃₂ and R₁₂ and wherein said intra-ring branched spacer is selected to form two rings selected from the group consisting of cycloalkyl having from 3 through 10 contiguous members, cycloalkenyl having from 5 through 10 contiguous members, and heterocyclyl having from 5 through 10 contiguous members;

[0034] R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the provisos that R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen, that no more than three of the R₃₃ and R₃₄ substituents are simultaneously selected from other than the group consisting of of hydrido and halo, and that no more than three of the R₃₅ and R₃₆ substituents are simultaneously selected from other than the group consistubg of hydrido and halo;

[0035] R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are independently selected to be oxo with the provisos that B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C and S, no more than two of R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are simultaneously oxo, and that R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

[0036] R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, are used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ are used at the same time;

[0037] R₉ and R₁₁, R₉ and R₁₂, R₉ and R₁₃, R₉ and R₃₁, R₉ and R₃₂, R₁₀ and R₁₂, R₁₀ and R₁₃, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₁ and R₁₂, R₁₁ and R₁₃, R₁₁ and R₃₂, R₁₂ and R₃₁, R₁₃ and R₃₁, and R₁₃ and R₃₂ are independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from 1 through 3 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, a saturated heterocyclyl having from 5 through 8 contiguous members and a partially saturated heterocyclyl having from 5 through 8 contiguous members with the provisos that no more than one of said group of spacer pairs is used at the same time;

[0038] R₃₇ and R₃₈ are independently selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, hydroxy, amino, thio, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, cyano, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.

[0039] In another embodiment of compounds of Formula I-WA, compounds are alcohols and have the Formula I-WO (also referred to herein as “alicyclic/cyclic aryl/heteroaryl aminoalkanols”):

[0040] or a pharmaceutically acceptable salt thereof, wherein;

[0041] R₁₆ is hydrido;

[0042] R₁, R₂, R₃, n, A, Y, Q, and Z are defined as given above for Formula I-WA.

[0043] In a more specific embodiment of compounds of Formula I-WO, compounds have the Formula I-WOPA:

[0044] or a pharmaceutically acceptable salt thereof, wherein;

[0045] n is an integer selected from 1 through 2;

[0046] A is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, C3-C8 haloalkenyl, C3-C6 alkoxy C1-C2 alkyl, and C3-C8 hydroxyhaloalkyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond;

[0047] R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl;

[0048] R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl;

[0049] R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl;

[0050] Y and Z are independently selected from the group consisting of a covalent single bond, oxy and alkylene;

[0051] R₄ and R₈ are independently selected from the group consisting of hydrido and halo;

[0052] R₅, R₆, and R₇ are independently selected from the group consisting of hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl;

[0053] R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time;

[0054] R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group group consisting of alkyl, halo, hydroxy, cyano, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl.

[0055] In another more specific embodiment of compounds of Formula I-WO, compounds have the Formula I-WOPC:

[0056] or a pharmaceutically acceptable salt thereof, wherein;

[0057] n is an integer selected from 1 through 2;

[0058] A is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁;

[0059] R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl;

[0060] R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl;

[0061] R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl;

[0062] Y and Z are independently selected from the group consisting of a covalent single bond, oxy and alkylene;

[0063] R₄ and R₈ are independently selected from the group consisting of hydrido and halo;

[0064] R₉ and R₁₃ is halo;

[0065] R₅, R₆, and R₇ are independently selected from the group consisting of hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl;

[0066] R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time;

[0067] R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ are independently selected from the group group consisting of alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl;

[0068] R₃₀ is selected from the group consisting of alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.

[0069] In another more specific embodiment of compounds of Formula I-WO, compounds have the Formula I-WOHA:

[0070] or a pharmaceutically acceptable salt thereof, wherein;

[0071] n is an integer selected from 1 through 2;

[0072] A is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, C3-C8 haloalkenyl, C3-C6 alkoxy C1-C2 alkyl, and C3-C8 hydroxyhaloalkyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond;

[0073] D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ is a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ is O, no more than one of D₁, D₂, J₁, J₂ and K₁ is S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K, are N;

[0074] R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl;

[0075] R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl;

[0076] R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl;

[0077] Y and Z are independently selected from the group consisting of a covalent single bond, oxy and alkylene;

[0078] R₄ and R₈ are independently selected from the group consisting of hydrido and halo;

[0079] R₅, R₆, and R₇ are independently selected from the group consisting of hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl;

[0080] R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time;

[0081] R₃₃, R₃₄,R₃₅, and R₃₆ are independently selected from the group group consisting of alkyl, halo, hydroxy, cyano, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl.

[0082] In still another more specific embodiment of compounds of Formula I-WO, compounds have the Formula I-WOHC:

[0083] or a pharmaceutically acceptable salt thereof, wherein;

[0084] n is an integer selected from 1 through 2;

[0085] A is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁;

[0086] D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ is a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ is O, no more than one of D₁, D₂, J₁, J₂ and K₁ is S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ are N;

[0087] R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl;

[0088] R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl;

[0089] R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl;

[0090] Y and Z are independently selected from the group consisting of a covalent single bond, oxy and alkylene;

[0091] R₄ and R₈ are independently selected from the group consisting of hydrido and halo;

[0092] R₉ and R₁₃ is halo;

[0093] R₅, R₆, and R₇ are independently selected from the group consisting of hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl;

[0094] R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time;

[0095] R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ are independently selected from the group group consisting of alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl;

[0096] R₃₀ is selected from the group consisting of alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.

[0097] In a preferred specific embodiment of compounds of Formulas I-WOPA, I-WOHA, I-WOPC, and I-WOHC,

[0098] n is the integer 1;

[0099] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0100] R₂ is selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, vinyl, phenyl, 4-trifluoromethylphenyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl;

[0101] R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, ethyl, vinyl, trifluoromethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0102] Y and Z are independently selected from the group consisting of a covalent single bond, oxy, and methylene with the proviso that only one of Y and Z are simultaneously oxy;

[0103] R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro;

[0104] R₅ is selected from the group consisting of 4-aminophenoxy, benzoyl, benzyl, benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-bromo-2-nitrophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-butoxyphenoxy, chloro, 3-chlorobenzyl, 2-chlorophenoxy, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro-fluorobenzyl, 3-chloro-4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chloro-3-methylphenoxy, 2-chloro-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro~ethylphenoxy, 3-chloro-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, cyclobutoxy, cyclobutyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropyl, cyclopropylmethoxy, cyclopropoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5difluorophenoxy, 3,4-difluorophenyl, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, fluoro, 4-fluoro-3-methylbenzyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methylbenzoyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-3-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, 3-iodobenzyloxy, isobutyl, isobutylamnino, isobutoxy, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxycarbonylbutoxy, 3-methoxycarbonylprop-2-enyloxy, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, phenylsulfonyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoromethylthio;

[0105] R₆ is selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, trifluoromethyl, and trifluoromethoxy;

[0106] R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl.

[0107] In a more preferred specific embodiment of compounds of Formulas I-WOPA, I-WOHA, I-WOPC, and I-WOHC,

[0108] n is the integer 1;

[0109] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0110] R₂ is selected from the group consisting of hydrido, methyl, ethyl, phenyl, 4-trifluoromethylphenyl, trifluoromethoxymethyl, 1,1,2,2-tetrafluoroethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl; R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl;

[0111] Y and Z are independently selected from a covalent single bond and methylene;

[0112] R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro;

[0113] R₅ is selected from the group consisting of benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromophenoxy, 4-butoxyphenoxy, 3-chlorobenzyloxy, 2-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, cyclobutoxy, cyclobutyl, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropylmethoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy,2,3-difluorobenzyloxy, 3,5-difluorobenzyloxy, difluoromethoxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy,3-dimethylaminophenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 1,3-dioxolan-2-yl, 3-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5methylphenoxy, 4-fluoro-3-methylbenzyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-3-trimethylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, isobutoxy, isobutyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, 3-isopropylbenzyloxy, 3-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenxyloxy, 3-methylphenoxy, 3-methyl-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3,4,5trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, 3-trifluoromethylthiobenzyloxy, and trifluoromethylthio;

[0114] R₆ is selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl;

[0115] R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl.

[0116] In an even more preferred specific embodiment of compounds of Formulas I-WOPA, I-WOHA, I-WOPC, and I-WOHC,

[0117] n is the integer 1;

[0118] R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0119] R₂ is hydrido, pentafluoroethyl, and trifluoromethyl;

[0120] R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl

[0121] Y and Z are independently selected from the group consisting of a covalent single bond and methylene;

[0122] R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro;

[0123] R₅ is selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1, 1, 2, 2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy), trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy;

[0124] R₆ is selected from the group consisting of fluoro and hydrido;

[0125] R₇ is selected from the group consisting of hydrido and fluoro.

[0126] In a preferred specific embodiment of compounds of Formulas I-WOPA and I-WOHA,

[0127] A is selected from the group consisting of ethyl, 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl~pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-5-hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 2-octyl, 1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptynyl, 1-methyl-3-heptynyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl4-heptenyl, 1-methyl-2-heptenyl, 1-methyl-3-heptynyl, 1-methyl-4-heptynyl, 1-methyl-5-heptynyl, 3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-5-hexenyl, 1-ethyl-2-hexynyl, 1-ethyl-3-hexynyl, 1-ethyl4-hexynyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-propyl-2-pentynyl, 1-propyl-3-pentynyl, 1-butyl-2-butynyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, 3,3,3-trifluoropropyl, 2-methoxyethyl, 2-ethoxyethyl, 2-propoxyethyl, 2-isopropoxyethyl, 2-butoxyethyl, 2-isobutoxyethyl, 2-sec-butoxyethyl, 2-pentoxyethyl, 2-hexoxyethyl, 3-methoxypropyl, 2-methoxyisopropyl, 3-ethoxypropyl, 2-ethoxyisopropyl, 3-propoxypropyl, 2-propoxyisopropyl, 3-isopropoxypropyl, 2-isopropoxyisopropyl, 3-butoxypropyl, 2-butoxyisopropyl, 3-isobutoxypropyl, 2-isobutoxyisopropyl, 3-pentoxypropyl, and 2-pentoxyisopropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond;

[0128] R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of cyano, hydroxy, 4-aminophenoxy, benzoyl, benzyl, benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-bromo-2-nitrophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-butoxyphenoxy, chloro, 3-chlorobenzyl, 2-chlorophenoxy, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro-4-fluorobenzyl, 3-chloro-4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chloro-3-methylphenoxy, 2-chloro-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, cyclobutoxy, cyclobutyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropyl, cyclopropylmethoxy, cyclopropoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, fluoro, 4-fluoro-3-methylbenzyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methylbenzoyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro4-trifluoromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, 3-iodobenzyloxy, isobutyl, isobutylamino, isobutoxy, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxycarbonylbutoxy, 3-methoxycarbonylprop-2-enyloxy, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, phenylsulfonyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1, 1, 2, 2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4yl, thiazol-5-yl, thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoromethylthio.

[0129] In a preferred specific embodiment of compounds of Formulas I-WOPA and I-WOHA,

[0130] A is selected from the group consisting of ethyl, 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5octenyl, 6octenyl, 7-octenyl, 2-octyl, 1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-4-heptenyl, 1-methyl4-heptenyl, 1-methyl-2-heptenyl, 3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-hexenyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond;

[0131] R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromophenoxy,4-butoxyphenoxy, 3-chlorobenzyloxy, 2-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloromethylphenoxy, 3-chloro-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, cyclobutoxy, cyclobutyl, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropylmethoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy,2,3-difluorobenzyloxy, 3,5-difluorobenzyloxy, difluoromethoxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy,3-dimethylaminophenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 1,3-dioxolan-2-yl, 3-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylbenzyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-trifluoromethylphenoxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, isobutoxy, isobutyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, 3-isopropylbenzyloxy, 3-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenxyloxy, 3-methylphenoxy, 3-methyl-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-yl, thiazol-5-yl, thiophen-2-yl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, 3-trifluoromethylthiobenzyloxy, and trifluoromethylthio.

[0132] In an even more preferred specific embodiment of compounds of Formulas I-WOPA and I-WOHA,

[0133] A is selected from the group consisting of 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl4-hexenyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3, 3, 3-trifluoropropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond;

[0134] R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy),trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy.

[0135] In a preferred specific embodiment of compounds of Formulas I-WOHA and I-WOHC,

[0136] D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 1,2,4-triazol-3-yl, 1, 2, 4-triazol-5yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazintyl, 1-indolizinyl, 7-indolizinyl, 1-isoquinolyl, and 2-quinolyl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R5, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆.

[0137] In a more preferred specific embodiment of compounds of Formulas I-WOHA and I-WOHC,

[0138] D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl. 1,3 ,Striazin-2-yl, 1-indolizinyl, 7-indolizinyl, 1-isoquinolyl, and 2-quinolyl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R₅, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆.

[0139] In an even more preferred specific embodiment of compounds of Formulas I-WOHA and I-WOHC,

[0140] D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R₅, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆.

[0141] In a preferred specific embodiment of compounds of Formulas I-WOPC and I-WOHC,

[0142] A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopent-2-enyl, cyclopent-3-enyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethyiphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cyclohex-2-enyl, cyclohex-3-enyl, cycloheptyl, cyclohept-2-enyl, cyclohept-3-enyl, cyclooctyl, cyclooct-2-enyl, cycloocl-3-enyl, cyclooct-4-enyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 2H-2-pyranyl, 2H-3-pyranyl, 2H-4-pyranyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-pyranyl, 2H-pyran-2-one-3-yl, 2H-pyran-2-one-4-yl, 2H-pyran-2-one-5-yl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁;

[0143] R₉ and R₁₃ are fluoro;

[0144] R₁₀ and R₁₂ are independently selected from the group consisting of 4-aminophenoxy, benzoyl, benzyl, benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-bromo-2-nitrophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-butoxyphenoxy, chloro, 3-chlorobenzyl, 2-chlorophenoxy, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro-fluorobenzyl, 3-chloro-4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, cyclobutoxy, cyclobutyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropyl, cyclopropylmethoxy, cyclopropoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, fluoro, 4-fluoro-3-methylbenzyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methylbenzoyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, 3-iodobenzyloxy, isobutyl, isobutylamino, isobutoxy, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxycarbonylbutoxy, 3-methoxycarbonylprop-2-enyloxy, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methylmethylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, phenylsulfonyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoromethylthio;

[0145] R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, trifluoromethyl, and trifluoromethoxy;

[0146] R₃₀ is selected from the group consisting of chloro, ethoxy, ethyl, fluoro, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, isobutyl, isobutoxy, isopropoxy, isopropyl, isopropylthio, methyl, propyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, propoxy, sec-butyl, tert-butoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, trifluoromethoxy, and trifluoromethyl.

[0147] In a more preferred specific embodiment of compounds of Formulas I-WOPC and I-WOHC,

[0148] A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cycloheptyl, cyclooctyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁;

[0149] R₉ and R₁₃ are fluoro;

[0150] R₁₀ and R₁₂ are independently selected from the group consisting of benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromophenoxy,4-butoxyphenoxy, 3-chlorobenzyloxy, 2-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, cyclobutoxy, cyclobutyl, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropylmethoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy,2,3-difluorobenzyloxy, 3,5-difluorobenzyloxy, difluoromethoxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy,3-dimethylaminophenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 1,3-dioxolan-2-yl, 3-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylbenzyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, isobutoxy, isobutyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, 3-isopropylbenzyloxy, 3-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenxyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-yl, thiazol-5-yl, thiophen-2-yl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, 3-trifluoromethylthiobenzyloxy, and trifluoromethylthio;

[0151] R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl;

[0152] R₃₀ is selected from the group consisting of chloro, ethyl, fluoro, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, isobutyl, isopropyl, methyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, propyl, sec-butyl, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, trifluoromethoxy, and trifluoromethyl.

[0153] In an even more preferred specific embodiment of compounds of Formulas I-WOPC and I-WOHC,

[0154] A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁;

[0155] R₉ and R₁₃ are fluoro;

[0156] R₁₀ and R₁₂ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy),trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy;

[0157] R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl.

DEFINITIONS

[0158] The use of generic terms in the description of the compounds are herein defined for clarity.

[0159] Standard single letter elemental symbols are used to represent specific types of atoms unless otherwise defined. The symbol “C” represents a carbon atom. The symbol “O” represents an oxygen atom. The symbol “N” represents a nitrogen atom. The symbol “P” represents a phosphorus atom. The symbol “S” represents a sulfur atom. The symbol “H” represents a hydrogen atom. Double letter elemental symbols are used as defined for the elements of the periodical table (i.e., Cl represents chlorine, Se represents selenium, etc.).

[0160] As utilized herein, the term “alkyl”, either alone or within other terms such as “haloalkyl” and “alkylthio”, means an acyclic alkyl radical containing from 1 to about 10, preferably from 3 to about 8 carbon atoms and more preferably 3 to about 6 carbon atoms. Said alkyl radicals may be optionally substituted with groups as defined below. Examples of such radicals include methyl, ethyl, chloroethyl, hydroxyethyl, n-propyl, oxopropyl, isopropyl, n-butyl, cyanobutyl, isobutyl, sec-butyl, tert-butyl, pentyl, aminopentyl, iso-amyl, hexyl, octyl and the like.

[0161] The term “alkenyl” refers to an unsaturated, acyclic hydrocarbon radical in so much as it contains at least one double bond. Such alkenyl radicals contain from about 2 to about 10 carbon atoms, preferably from about 3 to about 8 carbon atoms and more preferably 3 to about 6 carbon atoms. Said alkenyl radicals may be optionally substituted with groups as defined below. Examples of suitable alkenyl radicals include propenyl, 2-chloropropenyl, buten-1-yl, isobutenyl, penten-1-yl, 2-2-methylbuten-1-yl, 3-methylbuten-1-yl, hexen-1-yl, 3-hydroxyhexen-1-yl, hepten-1-yl, and octen-1-yl, and the like.

[0162] The term “alkynyl” refers to an unsaturated, acyclic hydrocarbon radical in so much as it contains one or more triple bonds, such radicals containing about 2 to about 10 carbon atoms, preferably having from about 3 to about 8 carbon atoms and more preferably having 3 to about 6 carbon atoms. Said alkynyl radicals may be optionally substituted with groups as defined below.

[0163] Examples of suitable alkynyl radicals include ethynyl, propynyl, hydroxypropynyl, butyn-1-yl, butyn-2-yl, pentyn-1-yl, pentyn-2-yl, 4-methoxypentyn-2-yl, 3-methylbutyn-1-yl, hexyn-1-yl, hexyn-2-yl, hexyn-3-yl, 3,3-dimethylbutyn-1-yl radicals and the like.

[0164] The term “hydrido” denotes a single hydrogen atom (H). This hydrido radical may be attached, for example, to an oxygen atom to form a “hydroxyl” radical, one hydrido radical may be attached to a carbon atom to form a “methine” radical (═CH—), or two hydrido radicals may be attached to a carbon atom to form a “methylene” (—CH₂—) radical.

[0165] The term “carbon” radical denotes a carbon atom without any covalent bonds and capable of forming four covalent bonds.

[0166] The term “cyano” radical denotes a carbon radical having three of four covalent bonds shared by a nitrogen atom.

[0167] The term “hydroxyalkyl” embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with a hydroxyl as defined above. Specifically embraced are monohydroxyalkyl, dihydroxyalkyl and polyhydroxyalkyl radicals.

[0168] The term “alkanoyl” embraces radicals wherein one or more of the terminal alkyl carbon atoms are substituted with one or more carbonyl radicals as defined below. Specifically embraced are monocarbonylalkyl and dicarbonylalkyl radicals. Examples of monocarbonylalkyl radicals include formyl, acetyl, and pentanoyl. Examples of dicarbonylalkyl radicals include oxalyl, malonyl, and succinyl.

[0169] The term “alkylene” radical denotes linear or branched radicals having from 1 about 10 carbon atoms and having attachment points for two or more covalent bonds. Examples of such radicals are methylene, ethylene, ethylidene, methylethylene, and isopropylidene.

[0170] The term “alkenylene” radical denotes linear or branched radicals having from 2 to about 10 carbon atoms, at least one double bond, and having attachment points for two or more covalent bonds. Examples of such radicals are 1,1-vinylidene (CH₂═C), 1,2-vinylidene (—CH═CH—), and 1,4-butadienyl (—CH═CH—CH═CH—).

[0171] The term “halo” means halogens such as fluorine, chlorine, bromine or iodine atoms.

[0172] The term “haloalkyl” embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have either a bromo, chloro or a fluoro atom within the radical. Dihalo radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred haloalkyl radicals are “lower haloalkyl” radicals having one to about six carbon atoms. Examples of such haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

[0173] The term “hydroxyhaloalkyl” embraces radicals wherein any one or more of the haloalkyl carbon atoms is substituted with hydroxy as defined above. Examples of “hydroxyhaloalkyl” radicals include hexafluorohydoxypropyl.

[0174] The term “haloalkylene radical” denotes alkylene radicals wherein any one or more of the alkylene carbon atoms is substituted with halo as defined above. Dihalo alkylene radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkylene radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred haloalkylene radicals are “lower haloalkylene” radicals having one to about six carbon atoms. Examples of “haloalkylene” radicals include difluoromethylene, tetrafluoroethylene, tetrachloroethylene, alkyl substituted monofluoromethylene, and aryl substituted trifluoromethylene.

[0175] The term “haloalkenyl” denotes linear or branched radicals having from 1 to about 10 carbon atoms and having one or more double bonds wherein any one or more of the alkenyl carbon atoms is substituted with halo as defined above. Dihaloalkenyl radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkenyl radicals may have more than two of the same halo atoms or a combination of different halo radicals.

[0176] The terms “alkoxy” and “alkoxyalkyl” embrace linear or branched oxy-containing radicals each having alkyl portions of one to about ten carbon atoms, such as methoxy radical. The term “alkoxyalkyl” also embraces alkyl radicals having one or more alkoxy radicals attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl radicals. More preferred alkoxy radicals are “lower alkoxy” radicals having one to six carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy, isopropoxy and tent-butoxy alkyls. The “alkoxy” radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide “haloalkoxy” and “haloalkoxyalkyl” radicals. Examples of such haloalkoxy radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, difluoromethoxy, trifluoroethoxy, fluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy, and fluoropropoxy. Examples of such haloalkoxyalkyl radicals include fluoromethoxymethyl, chloromethoxyethyl, trifluoromethoxymethyl, difluoromethoxyethyl, and trifluoroethoxymethyl.

[0177] The terms “alkenyloxy” and “alkenyloxyalkyl” embrace linear or branched oxy-containing radicals each having alkenyl portions of two to about ten carbon atoms, such as ethenyloxy or propenyloxy radical. The term “alkenyloxyalkyl” also embraces alkenyl radicals having one or more alkenyloxy radicals attached to the alkyl radical, that is, to form monoalkenyloxyalkyl and dialkenyloxyalkyl radicals. More preferred alkenyloxy radicals are “lower alkenyloxy” radicals having two to six carbon atoms. Examples of such radicals include ethenyloxy, propenyloxy, butenyloxy, and isopropenyloxy alkyls. The “alkenyloxy” radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide “haloalkenyloxy” radicals. Examples of such radicals include trifluoroethenyloxy, fluoroethenyloxy, difluoroethenyhloxy, and fluoropropenyloxy.

[0178] The term “haloalkoxyalkyl” also embraces alkyl radicals having one or more haloalkoxy radicals attached to the alkyl radical, that is, to form monohaloalkoxyalkyl and dihaloalkoxyalkyl radicals. The term “haloalkenyloxy” also embraces oxygen radicals having one or more haloalkenyloxy radicals attached to the oxygen radical, that is, to form monohaloalkenyloxy and dihaloalkenyloxy radicals. The term “haloalkenyloxyalkyl” also embraces alkyl radicals having one or more haloalkenyloxy radicals attached to the alkyl radical, that is, to form monohaloalkenyloxyalkyl and dihaloalkenyloxyalkyl radicals.

[0179] The term “alkylenedioxy” radicals denotes alkylene radicals having at least two oxygens bonded to a single alkylene group. Examples of “alkylenedioxy” radicals include methylenedioxy, ethylenedioxy, alkylsubstituted methylenedioxy, and arylsubstituted methylenedioxy. The term “haloalkylenedioxy” radicals denotes haloalkylene radicals having at least two oxy groups bonded to a single haloalkyl group. Examples of “haloalkylenedioxy” radicals include difluoromethylenedioxy, tetrafluoroethylenedioxy, tetrachloroethylenedioxy, alkylsubstituted monofluoromethylenedioxy, and arylsubstituted monofluoromethylenedioxy.

[0180] The term “aryl”, alone or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such rings may be attached together in a pendant manner or may be fused. The term “fused” means that a second ring is present (i.e., attached or formed) by having two adjacent atoms in common (i.e., shared) with the first ring. The term “fused” is equivalent to the term “condensed”. The term “aryl” embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl.

[0181] The term “perhaloaryl” embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl wherein the aryl radical is substituted with 3 or more halo radicals as defined below.

[0182] The term “heterocyclyl” embraces saturated and partially saturated heteroatom-containing ring-shaped radicals having from 5 through 15 ring members selected from carbon, nitrogen, sulfur and oxygen, wherein at least one ring atom is a heteroatom. Heterocyclyl radicals may contain one, two or three rings wherein such rings may be attached in a pendant manner or may be fused. Examples of saturated heterocyclic radicals include saturated 3 to 6-membered heteromonocylic group containing 1 to 4 nitrogen atoms[e.g. pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.]; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. morpholinyl, etc.]; saturated 3 to 6membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., thiazolidinyl, etc.]. Examples of partially saturated heterocyclyl radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole. Non-limiting examples of heterocyclic radicals include 2-pyrrolinyl, 3-pyrrolinyl, pyrrolindinyl, 1,3-dioxolanyl, 2H-pyranyl, 4H-pyranyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl, thiomorpholinyl, and the like.

[0183] The term “heteroaryl” embraces fully unsaturated heteroatom-containing ring-shaped aromatic radicals having from 5 through 15 ring members selected from carbon, nitrogen, sulfur and oxygen, wherein at least one ring atom is a heteroatom. Heteroaryl radicals may contain one, two or three rings wherein such rings may be attached in a pendant manner or may be fused. Examples of “heteroaryl” radicals, include unsaturated 5 to 6 membered heteromonocyclyl group containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl [e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.] tetrazolyl [e.g. 1H-tetrazolyl, 2H-tetrazolyl, etc.], etc.; unsaturated condensed heterocyclic group containing 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g., tetrazolo [1,5-b]pyridazinyl, etc.], etc.; unsaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, pyranyl, 2-furyl, 3-furyl, etc.; unsaturated 5 to 6membered heteromonocyclic group containing a sulfur atom, for example, 2-thienyl, 3-thienyl, etc.: unsaturated 5 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl [e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.] etc.; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. benzoxazolyl, benzoxadiazolyl, etc.]; unsaturated 5 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl [e.g., 1,2,4- thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.] etc.; unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., benzothiazolyl, benzothiadiazolyl, etc.] and the like. The term also embraces radicals where heterocyclic radicals are fused with aryl radicals. Examples of such fused bicyclic radicals include benzofuran, benzothiophene, and the like.

[0184] Said “heterocyclyl” group may have 1 to 3 substituents as defined below. Preferred heterocyclic radicals include five to twelve membered fused or unfused radicals. Non-limiting examples of heteroaryl radicals include pyrrolyl, pyridinyl, pyridyloxy, pyrazolyl, triazolyl, pyrimidinyl, pyridazinyl, oxazolyl, thiazolyl, imidazolyl, indolyl, thiophenyl, furanyl, tetrazolyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, pyrazinyl, piperazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, benzo(b)thiophenyl, benzimidazoyl, quinolinyl, tetraazolyl, and the like.

[0185] The term “sulfonyl”, whether used alone or linked to other terms such as alkylsulfonyl, denotes respectively divalent radicals —SO₂—. “Alkylsulfonyl”, embraces alkyl radicals attached to a sulfonyl radical, where alkyl is defined as above. “Alkylsulfonylalkyl”, embraces alkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. “Haloalkylsulfonyl”, embraces haloalkyl radicals attached to a sulfonyl radical, where haloalkyl is defined as above. “Haloalkylsulfonylalkyl”, embraces haloalkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. The term “aminosulfonyl” denotes an amino radical attached to a sulfonyl radical.

[0186] The term “sulfinyl”, whether used alone or linked to other terms such as alkylsulfinyl, denotes respectively divalent radicals —S(O)—. “Alkylsulfinyl”, embraces alkyl radicals attached to a sulfinyl radical, where alkyl is defined as above. “Alkylsulfinylalkyl”, embraces alkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above. “Haloalkylsulfinyl”, embraces haloalkyl radicals attached to a sulfinyl radical, where haloalkyl is defined as above. “Haloalkylsulfinylalkyl”, embraces haloalkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0187] The term “aralkyl” embraces aryl-substituted alkyl radicals. Preferable aralkyl radicals are “lower aralkyl” radicals having aryl radicals attached to alkyl radicals having one to six carbon atoms. Examples of such radicals include benzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylethyl. The terms benzyl and phenylmethyl are interchangeable.

[0188] The term “heteroaralkyl” embraces heteroaryl-substituted alkyl radicals wherein the heteroaralkyl radical may be additionally substituted with three or more substituents as defined above for aralkyl radicals. The term “perhaloaralkyl” embraces aryl-substituted alkyl radicals wherein the aralkyl radical is substituted with three or more halo radicals as defined above.

[0189] The term “aralkylsulfinyl”, embraces aralkyl radicals attached to a sulfinyl radical, where aralkyl is defined as above. “Aralkylsulfinylalkyl”, embraces aralkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0190] The term “aralkylsulfonyl”, embraces aralkyl radicals attached to a sulfonyl radical, where aralkyl is defined as above. “Aralkylsulfonylalkyl”, embraces aralkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0191] The term “cycloalkyl” embraces radicals having from 3 through 15 carbon atoms. Cycloalkyl radicals may contain one, two, three, or four rings wherein such rings may be attached in a pendant manner or may be fused. Examples of cycloalkyl radicals having two or more rings include adamantyl, norbornyl, and 7-oxabicyclo[2.2.1]heptanyl. More preferred cycloalkyl radicals are “lower cycloalkyl” radicals having from 3 through 8 carbon atoms. Examples include radicals such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The term “cycloalkyl” also embraces radicals where cycloalkyl radicals are fused with aryl radicals or heterocyclyl radicals. The term “cycloalkylalkyl” embraces cycloalkyl-substituted alkyl radicals. Preferable cycloalkylalkyl radicals are “lower cycloalkylalkyl” radicals having cycloalkyl radicals attached to alkyl radicals having from one through six carbon atoms. Examples of such radicals include cyclohexylhexyl. The term “cycloalkenyl” embraces radicals having three to fifteen carbon atoms and one or more carbon-carbon double bonds. Cycloalkenyl radicals may contain one, two, three, or four rings wherein such rings may be attached in a pendant manner or may be fused. Examples of cycloalkenyl radicals having two or more rings include norbornenyl. Preferred cycloalkenyl radicals are “lower cycloalkenyl” radicals having three to seven carbon atoms. Examples include radicals such as cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl. The term “halocycloalkyl” embraces radicals wherein any one or more of the cycloalkyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohalocycloalkyl, dihalocycloalkyl and polyhalocycloalkyl radicals. A monohalocycloalkyl radical, for one example, may have either a bromo, chloro or a fluoro atom within the radical. Dihalo radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhalocycloalkyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred halocycloalkyl radicals are “lower halocycloalkyl” radicals having three to about eight carbon atoms. Examples of such halocycloalkyl radicals include fluorocyclopropyl, difluorocyclobutyl, trifluorocyclopentyl, tetrafluorocyclohexyl, and dichlorocyclopropyl. The term “halocycloalkenyl” embraces radicals wherein any one or more of the cycloalkenyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohalocycloalkenyl, dihalocycloalkenyl and polyhalocycloalkenyl radicals.

[0192] The term “cycloalkoxy” embraces cycloalkyl radicals attached to an oxy radical. Examples of such radicals includes cyclohexoxy and cyclopentoxy. The term “cycloalkoxyalkyl” also embraces alkyl radicals having one or more cycloalkoxy radicals attached to the alkyl radical, that is, to form monocycloalkoxyalkyl and dicycloalkoxyalkyl radicals. Examples of such radicals include cyclohexoxyethyl. The “cycloalkoxy” radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide “halocycloalkoxy” and “halocycloalkoxyalkyl” radicals.

[0193] The term “cycloalkylalkoxy” embraces cycloalkyl radicals attached to an alkoxy radical. Examples of such radicals includes cyclohexylmethoxy and cyclopentylmethoxy.

[0194] The term “cycloalkenyloxy” embraces cycloalkenyl radicals attached to an oxy radical. Examples of such radicals includes cyclohexenyloxy and cyclopentenyloxy. The term “cycloalkenyloxyalkyl” also embraces alkyl radicals having one or more cycloalkenyloxy radicals attached to the alkyl radical, that is, to form monocycloalkenyloxyalkyl and dicycloalkenyloxyalkyl radicals. Examples of such radicals include cyclohexenyloxyethyl. The “cycloalkenyloxy” radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide “halocycloalkenyloxy” and “halocycloalkenyloxyalkyl” radicals.

[0195] The term “cycloalkylenedioxy” radicals denotes cycloalkylene radicals having at least two oxygens bonded to a single cycloalkylene group. Examples of “alkylenedioxy” radicals include 1,2-dioxycyclohexylene.

[0196] The term “cycloalkylsulfinyl”, embraces cycloalkyl radicals attached to a sulfinyl radical, where cycloalkyl is defined as above. “Cycloalkylsulfinylalkyl”, embraces cycloalkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above. The term “Cycloalkylsulfonyl”, embraces cycloalkyl radicals attached to a sulfonyl radical, where cycloalkyl is defined as above. “Cycloalkylsulfonylalkyl”, embraces cycloalkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0197] The term “cycloalkylalkanoyl” embraces radicals wherein one or more of the cycloalkyl carbon atoms are substituted with one or more carbonyl radicals as defined below. Specifically embraced are monocarbonylcycloalkyl and dicarbonylcycloalkyl radicals. Examples of monocarbonylcycloalkyl radicals include cyclohexylcarbonyl, cyclohexylacetyl, and cyclopentylcarbonyl. Examples of dicarbonylcycloalkyl radicals include 1,2-dicarbonylcyclohexane.

[0198] The term “alkylthio” embraces radicals containing a linear or branched alkyl radical, of one to ten carbon atoms, attached to a divalent sulfur atom. More preferred alkylthio radicals are “lower alkylthio” radicals having one to six carbon atoms. An example of “lower alkylthio” is methylthio (CH₃—S—). The “alkylthio” radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide “haloalkylthio” radicals. Examples of such radicals include fluoromethylthio, chloromethylthio, trifluoromethylthio, difluoromethylthio, trifluoroethylthio, fluoroethylthio, tetrafluoroethylthio, pentafluoroethylthio, and fluoropropylthio.

[0199] The term “alkyl aryl amino” embraces radicals containing a linear or branched alkyl radical, of one to ten carbon atoms, and one aryl radical both attached to an amino radical. Examples include N-methyltmethoxyaniline, N-ethyl-4-methoxyaniline, and N-methyl-4-trifluoromethoxyaniline.

[0200] The terms alkylamino denotes “monoalkylamino” and “dialkylamino” containing one or two alkyl radicals, respectively, attached to an amino radical.

[0201] The terms arylamino denotes “monoarylamino” and “diarylamino” containing one or two aryl radicals, respectively, attached to an amino radical. Examples of such radicals include N-phenylamino and N-naphthylamino.

[0202] The term “aralkylamino”, embraces aralkyl radicals attached to an amino radical, where aralkyl is defined as above. The term aralkylamino denotes “monoaralkylamino” and “diaralkylamino” containing one or two aralkyl radicals, respectively, attached to an amino radical. The term aralkylamino further denotes “monoaralkyl monoalkylamino” containing one aralkyl radical and one alkyl radical attached to an amino radical.

[0203] The term “arylsulfinyl” embraces radicals containing an aryl radical, as defined above, attached to a divalent S(═O) atom. The term “arylsulfinylalkyl” denotes arylsulfinyl radicals attached to a linear or branched alkyl radical, of one to ten carbon atoms.

[0204] The term “arylsulfonyl”, embraces aryl radicals attached to a sulfonyl radical, where aryl is defined as above. “arylsulfonylalkyl”, embraces arylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. The term “heteroarylsulfinyl” embraces radicals containing an heteroaryl radical, as defined above, attached to a divalent S(═O) atom. The term “heteroarylsulfinylalkyl” denotes heteroarylsulfinyl radicals attached to a linear or branched alkyl radical, of one to ten carbon atoms. The term “Heteroarylsulfonyl”, embraces heteroaryl radicals attached to a sulfonyl radical, where heteroaryl is defined as above. “Heteroarylsulfonylalkyl”, embraces heteroarylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0205] The term “aryloxy” embraces aryl radicals, as defined above, attached to an oxygen atom. Examples of such radicals include phenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 3-chloro-ethylphenoxy, 3,4-dichlorophenoxy, 4-methylphenoxy, 3-trifluoromethoxyphenoxy, 3-trifluoromethylphenoxy, 4-fluorophenoxy, 3,4-dimethylphenoxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-fluoro-3-methylphenoxy, 5,6,7,8-tetrahydronaphthyloxy, 3-isopropylphenoxy, 3-cyclopropylphenoxy, 3-ethylphenoxy, 4-tert-butylphenoxy, 3-pentafluoroethylphenoxy, and 3-(1,1,2,2-tetrafluoroethoxy)phenoxy.

[0206] The term “aroyl” embraces aryl radicals, as defined above, attached to an carbonyl radical as defined above. Examples of such radicals include benzoyl and toluoyl.

[0207] The term “aralkanoyl” embraces aralkyl radicals, as defined herein, attached to an carbonyl radical as defined above. Examples of such radicals include, for example, phenylacetyl.

[0208] The term “aralkoxy” embraces oxy-containing aralkyl radicals attached through an oxygen atom to other radicals. More preferred aralkoxy radicals are “lower aralkoxy” radicals having phenyl radicals attached to lower alkoxy radical as described above. Examples of such radicals include benzyloxy, 1-phenylethoxy, 3-trifluoromethoxybenzyloxy, 3-trifluoromethylbenzyloxy, 3,5-difluorobenyloxy, 3-bromobenzyloxy, 4-propylbenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, and 2-phenylethoxy.

[0209] The term “aryloxyalkyl” embraces aryloxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include phenoxymethyl.

[0210] The term “haloaryloxyalkyl” embraces aryloxyalkyl radicals, as defined above, wherein one to five halo radicals are attached to an aryloxy group.

[0211] The term “heteroaroyl” embraces heteroaryl radicals, as defined above, attached to an carbonyl radical as defined above. Examples of such radicals include furyl and nicotinyl.

[0212] The term “heteroaralkanoyl” embraces heteroaralkyl radicals, as defined herein, attached to an carbonyl radical as defined above. Examples of such radicals include, for example, pyridylacetyl and furylbutyryl.

[0213] The term “heteroaralkoxy” embraces oxy-containing heteroaralkyl radicals attached through an oxygen atom to other radicals. More preferred heteroaralkoxy radicals are “lower heteroaralkoxy” radicals having heteroaryl radicals attached to lower alkoxy radical as described above.

[0214] The term “haloheteroaryloxyalkyl” embraces heteroaryloxyalkyl radicals, as defined above, wherein one to four halo radicals are attached to an heteroaryloxy group.

[0215] The term “heteroarylamino” embraces heterocyclyl radicals, as defined above, attached to an amino group. Examples of such radicals include pyridylamino.

[0216] The term “heteroarylaminoalkyl” embraces heteroarylamino radicals, as defined above, attached to an alkyl group. Examples of such radicals include pyridylmethylamino.

[0217] The term “heteroaryloxy” embraces heterocyclyl radicals, as defined above, attached to an oxy group. Examples of such radicals include 2-thiophenyloxy, 2-pyrimidyloxy, 2-pyridyloxy, 3-pyridyloxy, and 4-pyridyloxy.

[0218] The term “heteroaryloxyalkyl” embraces heteroaryloxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include 2-pyridyloxymethyl, 3-pyridyloxyethyl, and 4-pyridyloxymethyl.

[0219] The term “arylthio” embraces aryl radicals, as defined above, attached to an sulfur atom. Examples of such radicals include phenylthio.

[0220] The term “arylthioalkyl” embraces arylthio radicals, as defined above, attached to an alkyl group. Examples of such radicals include phenylthiomethyl.

[0221] The term “alkylthioalkyl” embraces alkylthio radicals, as defined above, attached to an alkyl group. Examples of such radicals include methylthiomethyl. The term “alkoxyalkyl” embraces alkoxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include methoxymethyl.

[0222] The term “carbonyl” denotes a carbon radical having two of the four covalent bonds shared with an oxygen atom. The term “carboxy” embraces a hydroxyl radical, as defined above, attached to one of two unshared bonds in a carbonyl group. The term “carboxamide” embraces amino, monoalkylamino, dialkylamino, monocycloalkylamino, alkylcycloalkylamino, and dicycloalkylamino radicals, attached to one of two unshared bonds in a carbonyl group. The term “carboxamidoalkyl” embraces carboxamide radicals, as defined above, attached to an alkyl group. The term “carboxyalkyl” embraces a carboxy radical, as defined above, attached to an alkyl group. The term “carboalkoxy” embraces alkoxy radicals, as defined above, attached to one of two unshared bonds in a carbonyl group. The term “carboaralkoxy” embraces aralkoxy radicals, as defined above, attached to one of two unshared bonds in a carbonyl group. The term “monocarboalkoxyalkyl” embraces one carboalkoxy radical, as defined above, attached to an alkyl group. The term “dicarboalkoxyalkyl” embraces two carboalkoxy radicals, as defined above, attached to an alkylene group. The term “monocyanoalkyl” embraces one cyano radical, as defined above, attached to an alkyl group. The term “dicyanoalkylene” embraces two cyano radicals, as defined above, attached to an alkyl group. The term “carboalkoxycyanoalkyl” embraces one cyano radical, as defined above, attached to an carboalkoxyalkyl group.

[0223] The term “acyl”, alone or in combination, means a carbonyl or thionocarbonyl group bonded to a radical selected from, for example, hydrido, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkoxyalkyl, haloalkoxy, aryl, heterocyclyl, heteroaryl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, alkylthio, arylthio, amino, alkylamino, dialkylamino, aralkoxy, arylthio, and alkylthioalkyl. Examples of “acyl” are formyl, acetyl, benzoyl, trifluoroacetyl, phthaloyl, malonyl, nicotinyl, and the like. The term “haloalkanoyl” embraces one or more halo radicals, as defined herein, attached to an alkanoyl radical as defined above. Examples of such radicals include, for example, chloroacetyl, trifluoroacetyl, bromopropanoyl, and heptafluorobutanoyl. The term “diacyl”, alone or in combination, means having two or more carbonyl or thionocarbonyl groups bonded to a radical selected from, for example, alkylene, alkenylene, alkynylene, haloalkylene, alkoxyalkylene, aryl, heterocyclyl, heteroaryl, aralkyl, cycloalkyl, cycloalkylalkyl, and cycloalkenyl. Examples of “diacyl” are phthaloyl, malonyl, succinyl, adipoyl, and the like.

[0224] The term “benzylidenyl” radical denotes substituted and unsubstituted benzyl groups having attachment points for two covalent bonds. One attachment point is through the methylene of the benzyl group with the other attachment point through an ortho carbon of the phenyl ring. The methylene group is designated for attached to the lowest numbered position. Examples include the base compound benzylidene of structure:

[0225] The term “phenoxylidenyl” radical denotes substituted and unsubstituted phenoxy groups having attachment points for two covalent bonds. One attachment point is through the oxy of the phenoxy group with the other attachment point through an ortho carbon of the phenyl ring. The oxy group is designated for attached to the lowest numbered position. Examples include the base compound phenoxylidene of structure:

[0226] The term “phosphono” embraces a pentavalent phosphorus attached with two covalent bonds to an oxygen radical. The term “dialkoxyphosphono” denotes two alkoxy radicals, as defined above, attached to a phosphono radical with two covalent bonds. The term “diaralkoxyphosphono” denotes two aralkoxy radicals, as defined above, attached to a phosphono radical with two covalent bonds. The term “dialkoxyphosphonoalkyl” denotes dialkoxyphosphono radicals, as defined above, attached to an alkyl radical. The term “diaralkoxyphosphonoalkyl” denotes diaralkoxyphosphono radicals, as defined above, attached to an alkyl radical.

[0227] Said “alkyl”, “alkenyl”, “alkynyl”, “alkanoyl”, “alkylene”, “alkenylene”, “benzylidenyl”, “phenoxylidenyl”, “hydroxyalkyl”, “haloalkyl”, “haloalkylene”, “haloalkenyl”, “alkoxy”, “alkenyloxy”, “alkenyloxyalkyl”, “alkoxyalkyl”, “aryl”, “perhaloaryl”, “haloalkoxy”, “haloalkoxyalkyl”, “haloalkenyloxy”, “haloalkenyloxyalkyl”, “alkylenedioxy”, “haloalkylenedioxy”, “heterocyclyl”, “heteroaryl”, “hydroxyhaloalkyl”, “alkylsulfonyl”, “haloalkylsulfonyl”, “alkylsulfonylalkyl”, “haloalkylsulfonylalkyl”, “alkylsulfinyl”, “alkylsulfinylalkyl”, “haloalkylsulfinylalkyl”, “aralkyl”, “heteroaralkyl”, “perhaloaralkyl”, “aralkylsulfonyl”, “aralkylsulfonylalkyl”, “aralkylsulfinyl”, “aralkylsulfinylalkyl”, “cycloalkyl”, “cycloalkylalkanoyl”, “cycloalkylalkyl”, “cycloalkenyl”, “halocycloalkyl”, “halocycloalkenyl”, “cycloalkylsulfinyl”, “cycloalkylsulfinylalkyl”, “cycloalkylsulfonyl”, “cycloalkylsulfonylalkyl”, “cycloalkoxy”, “cycloalkoxyalkyl”, “cycloalkylalkoxy”, “cycloalkenyloxy”, “cycloalkenyloxyalkyl”, “cycloalkylenedioxy”, “halocycloalkoxy”, “halocycloalkoxyalkyl”, “halocycloalkenyloxy”, “halocycloalkenyloxyalkyl”, “alkylthio”, “haloalkylthio”, “alkylsulfinyl”, “amino”, “oxy”, “thio”, “alkylamino”, “arylamino”, “aralkylamino”, “arylsulfinyl”, “arylsulfinylalkyl”, “arylsulfonyl”, “arylsulfonylalkyl”, “heteroarylsulfinyl”, “heteroarylsulfinylalkyl”, “heteroarylsulfonyl”, “heteroarylsulfonylalkyl”, “heteroarylamino”, “heteroarylaminoalkyl”, “heteroaryloxy”, “heteroaryloxylalkyl”, “aryloxy”, “aroyl”, “aralkanoyl”, “aralkoxy”, “aryloxyalkyl”, “haloaryloxyalkyl”, “heteroaroyl”, “heteroaralkanoyl”, “heteroaralkoxy”, “heteroaralkoxyalkyl”, “arylthio”, “arylthioalkyl”, “alkoxyalkyl”, “acyl” and “diacyl” groups defined above may optionally have 1 to 5 non-hydrido substituents such as perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarbonyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl.

[0228] The term “spacer” may include a covalent bond, a linear moiety having a backbone of 1 to 7 continous atoms, and a branched moiety having three branches connecting to a common atom with a total of from 1 through 8 atoms. The spacer may have 1 to 7 atoms of a univalent or multi-valent chain. Univalent chains may be constituted by a radical selected from ═C(H)—, ═C(R₁₇)—, —O—, —S—, —S(O)—, —S(O)₂—, —NH—, —N(R₁₇)—, —N═, —CH(OH)—, ═C(OH)—, —CH(OR₁₇)—, ═C(OR₁₇)—, and —C(O)— wherein R₁₇ is selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aryloxyalkyl, alkoxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkoxyalkyl, perhaloaralkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, and heteroarylalkenyl. Multi-valent chains may consist of a straight chain of 1 or 2 or 3 or 4 or 5 or 6 or 7 atoms, a straight chain of 1 or 2 or 3 or 4 or 5 or 6 atoms with a side chain, or a branched chain made up of 1 or 2 or 3 or 4 atoms in each of the three branches. The chain may be constituted of one or more radicals selected from: lower alkylene, lower alkenyl, —O—, —O—CH₂—, —S—CH₂—, —CH₂CH₂—, ethenyl, —CH═CH(OH)—, —OCH₂O—, —O(CH₂)₂O—, —NHCH₂—, —OCH(R₁₇)O—, —O(CH₂CHR₁₇)O—, —OCF₂O—, —O(CF₂)₂O—, —S—, —S(O)—, —S(O)₂—, —N(R)—, —N(H)O—, —N(R₁₇)O—, —N(R₁₇)—, —C(O)—, —C(O)NH—, —C(O)NR₁₇—, —N═, —OCH₂—, —SCH₂—, S(O)CH₂—, —CH₂C(O)—, —CH(OH)—, ═C(OH)—, —CH(OR₁₇)—, ═C(OR₁₇)—, S(O)₂CH₂—, and —NR₁₇CH₂— and many other radicals defined above or generally known or ascertained by one of skill-in-the art. Side chains may include substituents such as 1 to 5 non-hydrido substituents such as perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl.

[0229] Compounds of the present invention can exist in tautomeric, geometric or stereoisomeric forms. The present invention contemplates all such compounds, including cis- and trans-geometric isomers, E- and Z-geometric isomers, R- and S-enantiomers, diastereomers, d-isomers, 1-isomers, the racemic mixtures thereof and other mixtures thereof, as falling within the scope of the invention. Pharmaceutically acceptable sales of such tautomeric, geometric or stereoisomeric forms are also included within the invention.

[0230] The terms “cis” and “trans” denote a form of geometric isomerism in which two carbon atoms connected by a double bond will each have a hydrogen atom on the same side of the double bond (“cis”) or on opposite sides of the double bond (“trans”).

[0231] Some of the compounds described contain alkenyl groups, and are meant to include both cis and trans or “E” and “Z” geometric forms.

[0232] Some of the compounds described contain one or more stereocenters and are meant to include R, S, and mixtures of R and S forms for each stereocenter present.

[0233] Some of the compounds described herein may contain one or more ketonic or aldehydic carbonyl groups or combinations thereof alone or as part of a heterocyclic ring system. Such carbonyl groups may exist in part or principally in the “keto” form and in part or principally as one or more “enol” forms of each aldehyde and ketone group present. Compounds of the present invention having aldehydic or ketonic carbonyl groups are meant to include both “keto” and “enol” tautomeric forms.

[0234] Some of the compounds described herein may contain one or more amide carbonyl groups or combinations thereof alone or as part of a heterocyclic ring system. Such carbonyl groups may exist in part or principally in the “keto” form and in part or principally as one or more “enol” forms of each amide group present. Compounds of the present invention having amidic carbonyl groups are meant to include both “keto” and “enol” tautomeric forms. Said amide carbonyl groups may be both oxo (C═O) and thiono (C═S) in type.

[0235] Some of the compounds described herein may contain one or more imine or enamine groups or combinations thereof. Such groups may exist in part or principally in the “imine” form and in part or principally as one or more “enamine” forms of each group present. Compounds of the present invention having said imine or enamine groups are meant to include both “imine” and “enamine” tautomeric forms.

[0236] The following general synthetic sequences are useful in making the present invention. Abbreviations used in the schemes are as follows: “AA” represents amino acids, “BINAP” represents 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, “Boc” represents tert-butyloxycarbonyl, “BOP” represents benzotriazol-1-yl-oxy-tris-(dimethylamino), “bu” represents butyl, “dba” represents dibenzylideneacetone, “DCC” represents 1,3-dicyclohexylcarbodiimide, “DIBAH” represents diisobutylaluminum hydride, “DIPEA” represents diisopropylethylamine, “DMF” represents dimethylformamide, “DMSO” represents dimethylsulfoxide, “Fmoc” represents 9-fluorenylmethoxycarbonyl, “LDA” represents lithium diisopropylamide, “PHTH” represents a phthaloyl group, “pnZ” represents 4-nitrobenzyloxycarbonyl, “PTFC” represents a phase transfer catalyst, “p-TsOH” represents paratoluenesulfonic acid, “TBAF” represents tetrabutylammonium fluoride, “TBTU” represents 2-(1H-benzotriozole-1-yl)- 1,1,3,3-tetramethyl uronium tetrafluoroborate, “TEA” represents triethylamine, “TFA” represents trifluoroacetic acid, “THF” represents tetrahydrofuran, “TMS” represents trimethylsilyl, and “Z” represents benzyloxycarbonyl.

PHARMACEUTICAL UTILITY AND COMPOSITION

[0237] The present invention comprises a pharmaceutical composition comprising a therapeutically-effective amount of a compound of Formulas VII-H, VII, VII-2, VII-3, VII-4, and Cyclo-VII, in association with at least one pharmaceutically-acceptable carrier, adjuvant or diluent.

[0238] The present invention also comprises a treatment and prophylaxis of coronary artery disease and other CETP-mediated disorders in a subject, comprising administering to the subject having such disorder a therapeutically-effective amount of a compound of Formula I-WA:

[0239] wherein R₁, R₂, R₃, n, R₁₄, R₁₅, R₁₆, A, Q. X, Y, and Z are as defined above for the compounds of Formula I-WA;

[0240] or a pharmaceutically-acceptable salt thereof.

[0241] As a further embodiment, compounds of the present invention of Formulas I-WA, I-WO, I-WOHA, I-WOPC, I-WOHA, and I-WOHC, or a pharmaceutically-acceptable salt thereof as defined above and further comprise a treatment and prophylaxis of coronary artery disease and other CETP-mediated disorders in a subject, comprising administering to the subject having such disorder a therapeutically-effective amount of compounds of Formulas I-WA, I-WO, I-WOHA, I-WOPC, I-WOHA, and I-WOHC, of the present invention or a pharmaceutically-acceptable salt thereof.

[0242] Compounds of Formulas I-WA, I-WO, I-WOHA, I-WOPC, I-WOHA, and I-WOHC are capable of inhibiting activity of cholesteryl ester transfer protein (CEFP), and thus could be used in the manufacture of a medicament, a method for the prophylactic or therapeutic treatment of diseases mediated by CETP, such as peripheral vascular disease, hyperlipidaemia, hypercholesterolemia, and other diseases attributable to either high LDL and low HDL or a combination of both, or a procedure to study the mechanism of action of the cholesteryl ester transfer protein (CETP) to enable the design of better inhibitors. The compounds of Formulas I-WA, I-WO, I-WOHA, I-WOPC, I-WOHA, and I-WOHC would be also useful in prevention of cerebral vascular accident (CVA) or stroke.

[0243] Also included in the family of compounds of Formulas I-WA, I-WO, I-WOHA, I-WOPC, I-WOHA, and I-WOHC are the pharmaceutically-acceptable salts thereof. The term “pharmaceutically-acceptable salts” embraces salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not critical, provided that it is pharmaceutically acceptable. Suitable pharmaceutically-acceptable acid addition salts of compounds of Formula I-WA may be prepared from inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucoronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethylsulfonic, benzenesulfonic, sulfanilic, stearic, cyclohexylaminosulfonic, algenic, galacturonic acid. Suitable pharmaceutically-acceptable base addition salts of compounds of Formula I-WA include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N,N′-dibenzylethyleneldiamine, choline, chloroprocaine, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procain. All of these salts may be prepared by conventional means from the corresponding compounds of Formulas I-WA, I-WO, I-WOHA, I-WOPC, I-WOHA, and I-WOHC by reacting, for example, the appropriate acid or base with the compounds of Formulas I-WA, I-WO, I-WOHA, I-WOPC, I-WOHA, and I-WOHC.

[0244] Also embraced within this invention is a class of pharmaceutical compositions comprising the active compounds of Formula I-WA in association with one or more non-toxic, pharmaceutically-acceptable carriers and/or diluents and/or adjuvants (collectively referred to herein as “carrier” materials) and, if desired, other active ingredients. The active compounds of the present invention may be administered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended. The active compounds and composition may, for example, be administered orally, intravascularly, intraperitoneally, subcutaneously, intramuscularly or topically.

[0245] For oral administration, the pharmaceutical composition may be in the form of, for example, a tablet, capsule, suspension or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a particular amount of the active ingredient. Examples of such dosage units are tablets or capsules. The active ingredient may also be administered by injection as a composition wherein, for example, saline, dextrose or water may be used as a suitable carrier.

[0246] The amount of therapeutically active compounds which are administered and the dosage regimen for treating a disease condition with the compounds and/or compositions of this invention depends on a variety of factors, including the age, weight, sex and medical condition of the subject, the severity of the disease, the route and frequency of administration, and the particular compound employed, and thus may vary widely.

[0247] The pharmaceutical compositions may contain active ingredients in the range of about 0.1 to 2000 mg, and preferably in the range of about 0.5 to 500 mg. A daily dose of about 0.01 to 100 mg/kg body weight, and preferably between about 0.5 and about 20 mg/kg body weight, may be appropriate. The daily dose can be administered in one to four doses per day.

[0248] The compounds may be formulated in topical ointment or cream, or as a suppository, containing the active ingredients in a total amount of, for example, 0.075 to 30% w/w, preferably 0.2 to 20% w/w and most preferably 0.4 to 15% w/w. When formulated in an ointment, the active ingredients may be employed with either paraffinic or a water-miscible ointment base. Alternatively, the active ingredients may be formulated in a cream with an oil-in-water cream base. If desired, the aqueous phase of the cream base may include, for example at least 30% w/w of a polyhydric alcohol such as propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerol, polyethylene glycol and mixtures thereof. The topical formulation may desirably include a compound which enhances absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethylsulfoxide and related analogs. The compounds of this invention can also be administered by a transdermal device. Preferably topical administration will be accomplished using a patch either of the reservoir and porous membrane type or of a solid matrix variety. In either case, the active agent is delivered continuously from the reservoir or microcapsules through a membrane into the active agent permeable adhesive, which is in contact with the skin or mucosa of the recipient. If the active agent is absorbed through the skin, a controlled and predetermined flow of the active agent is administered to the recipient. In the case of microcapsules, the encapsulating agent may also function as the membrane.

[0249] The oily phase of the emulsions of this invention may be constituted from known ingredients in a known manner. While the phase may comprise merely an emulsifier, it may comprise a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts as a stabilizer. It is also preferred to include both an oil and a fat. Together, the emulsifier(s) with or without stabilizer(s) make-up the so-called emulsifying wax, and the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations. Emulsifiers and emulsion stabilizers suitable for use in the formulation of the present invention include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate, among others.

[0250] The choice of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the active compound in most oils likely to be used in pharmaceutical emulsion formulations is very low. Thus, the cream should preferably be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers. Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate or a blend of branched chain esters may be used. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and/or liquid paraffin or other mineral oils can be used.

[0251] For therapeutic purposes, the active compounds of this combination invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered per os, the compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapsulated for convenient administration. Such capsules or tablets may contain a controlled-release formulation as may be provided in a dispersion of active compound in hydroxypropylmethyl cellulose. Formulations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulations for oral administration. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various buffers. Other adjuvants and modes of administration are well and widely known in the pharmaceutical art.

[0252] All mentioned references are incorporated by reference as if here written.

[0253] Although this invention has been described with respect to specific embodiments, the details of these embodiments are not to be construed as limitations.

GENERAL SYNTHETIC PROCEDURES

[0254] The compounds of the present invention can be synthesized, for example, according to the following procedures of Schemes 1 through 14 below, wherein the substituents are as defined for Formulas I-WA, I-WO, I-WOHA, I-WOPC, I-WOHA, and I-WOHC above except where further noted.

[0255] Synthetic Scheme 1 shows the preparation of compounds of formula XIIIA-H (“Secondary Heteroaryl Amines”) which are intermediates in the preparation of the compounds of the present invention corresponding to Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) wherein one substituent (A or Q) on the nitrogen is AQ-1 which can be independently selected from the group consisting of aryl and heteroaryl, which are preferably substituted with one or more groups, and another substituent (A or Q) on the nitrogen is AQ-2 which can be independently selected from the group consisting of AQ-2 and —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H. AQ-2 and —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H can be independently selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, C3-C8 haloalkenyl, C3-C6 alkoxy C1-C2 alkyl, C3-C8 hydroxyhaloalkyl, C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4C9 saturated heterocyclyl, and C4C9 partially saturated heterocyclyl, wherein said group may be optionally substituted.

[0256] Schemes 1 through 14, taken together, prepare tertiary heteroalkylamine compounds of the present invention by addition of a halogenated, heteroatom (for example, oxygen, sulfur, or nitrogen) containing precursor to a resulting secondary amine to introduce a heteroatom containing alkyl group wherein one of the two groups making up the secondary amine is aromatic groups and the other is aliphatic (for example, C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, C3-C8 haloalkenyl, C3-C6 alkoxy C1-C2 alkyl, C3-C8 hydroxyhaloalkyl, C3-C10 cycloalkyl, C5-C10 cycloalkenyl), C4-C9 saturated heterocyclyl, and C4C9 partially saturated heterocyclyl.

[0257] The “Heteroaryl Imines” corresponding to Formulas XII-AH, CXII-AH, CKXII-AH can be prepared through dehydration techniques generally known in or adaptable from the art by reacting “Heteroaryl Amine” of Formula X-AH or a “Heteroaryl Carbonyl” of Formula XI-AH with a suitable an aliphatic, saturated heterocyclic, or partially saturated heterocyclic amine or carbonyl compound as shown in Schemes 1, 3, 4, 5, 6, 12, and subsequent specific examples. For example in Scheme 3, the two reactants (AQ-2A and XI-AH) react by refluxing them in an aprotic solvent, such as hexane, toluene, cyclohexane, benzene, and the like, using a Dean-Stark type trap to remove water. After about 2-8 hours or until the removal of water is complete, the aprotic solvent is removed in vacuo to yield the “Heteroaryl Imine” of Formula XII-AH.

[0258] The “Secondary Cyclic Heteroaryl Amines” of Formula XIIIA-H can be prepared from the corresponding “Generic Imine” of Formula XII, “Cyclic Heteroaryl Imine” of Formulas XII-AH, CXII-AH, and CKXII-AH can be prepared in several ways. For example, in one synthetic scheme (Reduction Method-1), the “Generic Imine” of Formula XII-AH is partially or completely dissolved in presence of a lower alcohol containing sufficient organic or mineral acid, as described in WO Patent Application No. 9738973, Swiss Patent CH 441366 and U.S. Pat. Nos. 3359316 and 3334017, which are incorporated herein by reference, and then hydrogenated at 0- 100° C., more preferably 20-50° C., and most preferably between 20-30° C. and pressures of 10-200 psi hydrogen or more preferably between 50-70 psi hydrogen in the presence of a noble metal catalyst such as PtO₂.

[0259] In another synthetic scheme (Reduction Method-2), the “Cyclic Heteroaryl Imine” of Formulas XII-AH, CXII-AH, and CKXII-AH is slurried in a lower alcohol such as ethanol, methanol or like solvent at 0-10° C. and solid sodium borohydride is added in batches over 5-10 minutes at 0-10° C. with stirring. The reaction mixture is stirred below 10° C. for 30-90 minutes and then is warmed gradually to 15-30° C. After about 1-10 hours, the mixture is cooled and acid is added until the aqueous layer was just acidic (pH 5-7).

[0260] In yet another synthetic scheme (Reduction Method-3), which is preferred when Z is an oxygen, the “Cyclic Heteroaryl Imine” of Formulas XII-AH, CXII-AH, and CKXII-AH is slurried in a lower alcohol solvent at 0-10° C. and acidified to a pH less than 4 and sodium cyanoborohydride is added in batches over 30-90 minutes at 0-20° C. with stirring and addition of a suitable organic or mineral acid to keep the pH at or below 4. The reaction mixture is stirred and warmed gradually to about 20-25° C. After about 1-10 hours, the mixture is cooled and base added until the mixture was just slightly alkaline.

[0261] The “Secondary Cyclic Heteroaryl Amines” of Formulas XIII-AH, CXIIIA-H, and CKXIII-AH can also be prepared, according to Schemes 1 and 3, by an alkylation procedure based on the nucleophilic substitution of bromides by amines. In one synthetic alkylation scheme (Alkylation Method-1), a “Cyclic Amine” of Formula AQ-2A or a “Generic Amine-I” of Formula X is reacted with a “Heteroaryl Bromide” of Formula XXI-AH or “Generic Bromide” of Formula XXI as described in Vogel's Textbook of Practical Organic Chemistry, Fifth Edition, 1989, pages 902 to 905 and references cited therein all of which are incorporated herein by reference. In an alternate synthetic alkylation scheme exemplified in Scheme 1, an “Amine” of Formula XXII is reacted with a “Heteroaryl Bromide” in a method employing palladium catalyzed carbon-nitrogen bond formation. Suitable procedures for this conversion are described in Wagaw and Buchwald, J. Org. Chem.(1996), 61, 7240-7241, Wolfe, Wagaw and Buchwald, J. Am. Chem. Soc. (1996), 118, 7215-7216, and Wolfe and Buchwald, Tetrahedron Letters (1997),38(36), 6359-6362 and references cited therein all of which are incorporated herein by reference.

[0262] The “Generic Secondary Amine”, “Heteroaryl Amine”, “Cyclic Amine”, “Alicyclic Amine”, and “Heteoaryl Hydroxylamine” amines and hydroxylamines, the “Generic Carbonyl”, “Heteroaryl Carbonyl”, “Cyclic Carbonyl”, and “Cyclic Ketone” aldehydes and ketones, and “Generic Bromide-1”, Generic Bromide-2”, “Heteroaryl Bromide”, and the like halides, tosylates, mesylates, triflates, and precursor alcohols required to prepare the “Secondary Cyclic Heteroaryl Amine” compounds are available from commercial sources or can be prepared by one skilled in the art from published procedures. Commercial sources include but are not limited to Aldrich Chemical, TCI-America, Lancaster-Synthesis, Oakwood Products, Acros Organics, and Maybridge Chemical. Disclosed procedures for “Generic Amine” amines, hydroxylamines, and hydrazines include Sheradsky and Nov, J. Chem. Soc., Perkin Trans.1 (1980), (12), 2781-6; Marcoux, Doye, and Buchwald, J.Am. Chem. Soc. (1997), 119, 1053-9; Sternbach and Jamison, Tetrahedron Lett. (1981), 22(35), 3331-4; U.S. Pat. No. 5306718; EP No. 314435; WO No. 9001874; WO No. 9002113; JP No. 05320117; WO No. 9738973; Swiss Patent No. CH 441366; U.S. Pat. Nos. 3359316 and 3334017; and references cited therein which are incorporated herein by reference.

[0263] Synthetic Schemes 2, 10 and 11 show the preparation of the class of compounds of the present invention corresponding to Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”).

[0264] Derivatives of “Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols” or “Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”, in which the heteroatom (O, N, or S) is attached to an alkyl group removed from the amine by two or more carbons are readily prepared by anion chemistry using the method of Scheme 2. The anion of “Secondary Amine” amines and hydroxylamines of Formula XIII are readily formed by dissolving the specific amine, hydroxylamine, or hydrazine in an aprotic solvent, such as tetrahydrofuran, toluene, ether, dimethylformamide, and dimethylformamide, under anhydrous conditions. The solution is cooled to a temperature between −78 and 0° C., preferably between −78 and −60° C. and the anion formed by the addition of at least one equivalent of a strong, aprotic, non-nucleophillic base such as NaH or n-butyllithium under an inert atmosphere for each acidic group present. Maintaining the temperature between −78 and 0° C., preferably between −78 and −60° C., with suitable cooling, an appropriate alkyl halide, alkyl benzenesulfonate such as a alkyl tosylate, alkyl mesylate, alkyl triflate or similar alkylating reagent of the general structure:

[0265] where m is zero, X can be RN, O, and S, and M is a readily displaceable group such as chloride, bromide, iodide, tosylate, triflate, and mesylate. After allowing the reaction mixture to warm to room temperature, the reaction product is added to water, neutralized if necessary, and extracted with a water-immiscible solvent such as diethyl ether or methylene chloride. The combined aprotic solvent extract is washed with saturated brine, dried over drying agent such as anhydrous MgSO₄ and concentrated in vacuo to yield crude Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”). This material is purified, for example, by eluting through silica gel with a medium polar solvent such as ethyl acetate in a non-polar solvent such as hexanes to yield purified Formula I-WA and Formula I-WO. Products are structurally confirmed by low and high resolution mass spectrometry and NMR.

[0266] Compounds of Formula (XXX), which can be used to prepare I-WA, I-WO, I-WOPA, I-WOPC, I-WOHA, and I-WOHC, are given in Table 2.

[0267] Reagents 1a and 2a in Table 2 are prepared from the corresponding alcohols. The tosylates are readily obtained by reacting the corresponding alcohol with tosyl chloride using procedures found in House's Modern Synthetic Reactions, Chapter 7, W. A. Benjamin, Inc., Shriner, Fuson, and Curtin in The Systematic Indentification of Organic Compounds, 5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents for Organic Synthesis, Volume 1, John Wiley & Sons, which are incorporated herein by reference.

[0268] A preferred procedure for Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines” compounds is Method A of Schemes 2, 10, 11, and 14. Oxirane reagents useful in Method A are exemplified, but not limited to those in Table 1. Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl 1-Amino-2-alcohol”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary 2-Heteroalkylamine”) compounds are prepared by using “Secondary Cyclic Heteroaryl Amine” and “Alicyclic Heteroaryl Amine” amines and hydroxylamines of Formulas XIIIA-H, CXIIIA-H, CKXIII-AH, ACXIIIA-H, and RACXIIIA-H prepared above with oxiranes of the type listed in Table I and represented by the general structure:

[0269] In some cases, the oxiranes are prepared by reaction of epoxidation reagents such as MCPBA and similar type reagents readily selectable by a person of skill-in-the-art with alkenes. Fieser and Fieser in Reagents for Organic Synthesis, John Wiley & Sons provides, along with cited references, numerous suitable epoxidation reagents and reaction conditions, which are incorporated herein by reference.

[0270] Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary 2-Heteroalkylamine”) compounds, wherein the 2-hetero group is an amino, substituted amino, or thiol, can be prepared by using appropriate aziridines and thirranes according to Method A of Scheme 2. Aziridine and thiirane reagents useful in Method A are exemplified, but not limited to those in Table 1. These Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary 2-Heteroalkylamine”) compounds, wherein the 2-hetero group is an amino, substituted amino, or thiol, can be prepared by using “Secondary Cyclic Heteroaryl Amine” and “Alicyclic Heteroaryl Amine” amines and hydroxylamines of Formulas XIIIA-H, CXIIIA-H, CKXIII-AH, ACXIIIA-H, and RACXIIIA-H prepared above with aziridines and thiiranes of the type listed in Table 1 and represented by the general structure:

[0271] wherein X is selected from N and S and R₁₆ is hydrogen or another suitable group when X is N. TABLE 1 Structure of Oxirane, Aziridine, and Thiirane Reagents. (XX)

Rgnt No. R₁₆ X R₁ R₂ R₃  1 — O CF₃ H H  2 — O CCl₃ H H  3 — O CF₃ CH₃ H  4 — O CF₃CF₂ H H  5 — O CF₃CF₂CF₂ H H  6 — O CF₃OCF₂CF₂ H H  7 — O CF₃CH₂ H H  8 — O CF₃ CHF₂ H  9 — O CF₃ H CF₃ 10 — O CF₃ CF₃ H 11 — O CF₃ C₆H₅ H 12 — O CCl₃ C₆H₅ H 13 — O CCl₃ Cyclopropyl H 14 — O CCl₃ CH₃ H 15 — O CCl₃ (CH₃)₂CH H 16 — O CHCl₂ H H 17 — O CHCl₂ Cl H 18 — O CF₃ H CH₃ 19 H N CF₃ CF₃ H 20 H N CF₃ H H 21 Benzyl N CF₃ H H 22 CH₃O N CF₃ H H 23 CH₃ N CF₃ H H 24 Benzyloxy N CF₃ H H 25 — S CF₃ H H 26 — S CF₃CF₂ H H 27 — O CCl₃CH₂ H H 28 — O CBr₃CH₂ H H 29 — O CHBr₂CH₂ H H 30 — O CBrCl₂ H H 31 — O CClF₂ H H 32 — O CCl₂F H H 33 — O CCl₃CCl₂ H H 43 — O FCH₂ H H 46 — O CF₃ R₂ + R₃ = (CH₂)₃ 47 — O CF₃ R₂ + R₃ = (CH₂)₄ 48 — O CHF₂ R₂ + R₃ = (CH₂)₄ 56 — O CBrF₂CClFCH₂ H H 57 — O HCF₂CF₂OCH₂ H H

[0272] TABLE 2 Structure and Source of Alcohol and Glycol Reagents. (XXX)

Reagent Number R₁ n M R₂ R₃ X-R₁₆ Source of Reagent 1A CF₃ 3 OTs H H OH Chiral separation and then tosylation of alcohol from Justus Liebigs Ann. Chem. (1969), 720, 81-97. 2A CF₃CH₂CH₂ 3 OTs H H OH Chiral separation and then tosylation of alcohol from Z. Naturforsch., B: Chem. Sci. (1997), 52 (3). 413-418

[0273] A mixture of a “Secondary Amine” amine or hydroxylamine and an oxirane of Formula XX are stirred and heated to 40-90° C. for 5 to 48 hours in a tightly capped or contained reaction vessel. A Lewis acid such as ytterbium triflate in acetonitrile may be added to speed up reaction and improve yield. When a Lewis acid is used, the reaction should be carried out under inert, anhydrous conditions using a blanket of dry nitrogen or argon gas. After cooling to room temperature and testing the reaction mixture for complete reaction by thin layer chromatography or high pressure liquid chromatography (hplc), the reaction product is added to water and extracted with a water immiscible solvent such as diethyl ether or methylene chloride. (Note: If the above analysis indicates that reaction is incomplete, heating should be resumed until complete with the optional addition of more of the oxirane). The combined aprotic solvent extract is washed with saturated brine, dried over drying agent such as anhydrous MgSO₄ and concentrated in vacuo to yield crude Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds. This material is purified by eluting through silica gel with 5-40% of a medium polar solvent such as ethyl acetate in a non-polar solvent such as hexanes to yield the Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds. Products are tested for purity by HPLC. If necessary, the Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds are purified by additional chromatography or recrystallization. Products are structurally confirmed by low and high resolution mass spectrometry and NMR. Examples of specific Formula VII Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) prepared are summarized in the Examples and Example Tables 1 through 7.

[0274] Specific Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) analogs of the Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds summarized in the Examples and Example Tables 1 through 7, wherein the hydroxyl or oxy group are replaced with an amino, substituted amino, aza, or thiol, can be prepared by using the appropriate aziridine reagents or thiirane reagents readily by adapting the procedures in the numerous specific Examples and Schemes disclosed in the present invention. Similarly, intermediates, in which the hydroxyl or oxy group of said intermediates are replaced with an amino, substituted amino, aza, or thiol, can be converted using the numerous specific Examples and Schemes disclosed in the present invention to other Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula 1-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds.

[0275] Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula 1-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds can further be prepared in an alternate manner to procedures disclosed above and in Schemes 1, 2, and 3. Schemes 12 and 13 detail such procedures to prepare compounds of the present invention by initial formation of an halogenated, oxygen containing primary alkylamine XL (“Generic Substituted Alkylamine”). Said halogenated, oxygen containing primary alkylamine XL, formed in Scheme 12, is itself converted to secondary amine LX-H (“Heteroaryl Alkyl Amine”) using procedures disclosed above. Primary alkylamine XL is first reacted with an aldehydic or ketonic carbonyl compound, XI-AH (“Heteroaryl Carbonyl”) with azeotropic distillation to form imines, L-H (“Heteroaryl Imine”). Said imine L-H are then reduced with or without prior isolation by Reduction Methods 1, 2 or 3 as disclosed above and in Scheme 1 to yield secondary amines LX-H (“Heteroaryl Alkyl Amine”). Said secondary amine LX-H can be converted according to Scheme 14 to Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”).

[0276] Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds can further be prepared in an alternate manner to procedures disclosed above and in additional Schemes.

[0277] Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) are alternately referred to as Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl 2-hydroxyalkylamines”).

[0278] Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds can themselves serve as intermediates for conversion to additional compounds of this invention. Compounds of the present invention useful as intermediates include those in which the R₅ or R₇ position substituent in Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) compounds is a bromo group, hydroxyl group, sulfhydryl group, bromomethyl or other bromoalkyl groups, nitro group, amino group, methoxy carbonyl or other alkoxy carbonyl groups, cyano group, or acyl groups. Other preferred compounds of the present invention useful as intermediates include those in which the R₁₀ position substituent in Formulas I-WA or I-WO is a bromo group, hydroxyl group, sulfhydryl group, bromomethyl or other bromoalkyl groups, nitro group, amino group, methoxy carbonyl or other alkoxy carbonyl groups, cyano group, or acyl groups. Other compounds of Formulas I-WA or I-WO and the present invention useful as intermediates include those in which one or more of R₆, R₁₁, and R₁₂ substituents in Formulas I-WA or I-WO is a bromo group, hydroxyl group, sulfhydryl group, bromomethyl or other bromoalkyl groups, nitro group, amino group, methoxy carbonyl or other alkoxy carbonyl groups, cyano group, or acyl groups.

[0279] Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) are alternately referred to as Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Tertiary 2-hydroxyalkylamines”).

[0280] A 3-bromo substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Bromoaryl Tertiary 2-Hydroxyalkylamines”) can be reacted with a phenol to afford 3-phenoxy compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Phenoxyaryl Tertiary 2-Hydroxyalkylamines”).

[0281] A 3-bromo substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Bromoheteroaryl Tertiary 2-hydroxyalkylamine”) can, be reacted, for example, with a phenol to afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Aryloxyaryl, 3-Heteroaryloxyaryl, 3-Heteroaryloxyheteroaryl, and 3-Aryloxyheteroaryl Tertiary 2-Hydroxyalkylamines”).

[0282] A 3-bromo substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Bromoaryl Tertiary 2-hydroxyalkylamine”) can be reacted with a phenol to afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Phenylaryl Tertiary 2-Hydroxyalkylamine”).

[0283] Conversion of a 3-bromo substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Bromoaryl Tertiary 2-hydroxyalkylamine”) by reaction with a primary or secondary amine can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3- R₂₂aminoaryl Tertiary 2-Hydroxyalkylamine”).

[0284] Conversion of a 3-bromo substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Bromoaryl Tertiary 2-hydroxyalkylamine”) by reaction with an aryl borinate can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Phenylaryl Tertiary 2-Hydroxyalkylamine”).

[0285] Conversion of a 3-bromo substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Bromoaryl Tertiary 2-hydroxyalkylamine”) by reaction with a heteroaryl dibutyl tin compound can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Heteroarylaryl Tertiary 2-Hydroxyalkylamine”).

[0286] Conversion of a 3-bromomethyl substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Bromomethylaryl Tertiary 2-hydroxyalkylamine”) by reaction with an aryl borinate can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Arylmethylaryl Tertiary 2-Hydroxyalkylamine”).

[0287] Conversion of a 3-hydroxyl substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Hydroxyheteroaryl Tertiary 2-hydroxyalkylamine”) by reaction with an aryl bromide or heteroaryl bromide can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Aryloxyaryl, 3-Heteroaryloxyaryl, 3-Heteroaryloxyheteroaryl, and 3-Aryloxyheteroaryl Tertiary 2-Hydroxyalkylamines”).

[0288] Conversion of a 3-hydroxyl substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Hydroxyaryl Tertiary 2-hydroxyalkylamine”) by reaction with an aryl bromide can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Phenoxyaryl Tertiary 2-Hydroxyalkylamine”).

[0289] Conversion of a 3-hydroxyl substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Hydroxyheteroaryl Tertiary 2-hydroxyalkylamine”) by reaction with an aralkyl bromide or heteroaralkyl bromide can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Aralkyloxyaryl, 3-Heteroaralkyloxyaryl, 3-Heteroaralkyloxyheteroaryl, and 3-Aralkyloxyheteroaryl Tertiary 2-Hydroxyalkylamines”).

[0290] Conversion of a 3-hydroxyl substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Hydroxyaryl Tertiary 2-hydroxyalkylamine”) by reaction with an aralkyl bromide can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Aralkyloxyaryl Tertiary 2-Hydroxyalkylamine”).

[0291] Conversion of a 3-hydroxyl substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic Polycyclic 3-Hydroxyaryl Tertiary 2-hydroxyalkylamine”) by reaction with a displaceable organo bromide can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Organooxyaryl Tertiary 2-Hydroxyalkylamine”).

[0292] Conversion of a 3-thio substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-thioaryl Tertiary 2-hydroxyalkylamine”) by reaction with a displaceable organo bromide can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Organothiaaryl Tertiary 2-Hydroxyalkylamine”). “Alicyclic/Cyclic 3-Organothiaaryl Tertiary 2-Hydroxyalkylamines” can be oxidized to sulfonyl compounds of 3-Organosulfonylaryl Tertiary 2-Hydroxyalkylamine”).

[0293] Conversion of a 3-nitro substituent at the R₅ position in Formula l-WO (“Alicyclic/Cyclic 3-Nitroaryl Tertiary 2-hydroxyalkylamine”) by hydrogenation can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Amninoaryl Tertiary 2-Hydroxyalkylamine”). Formula I-WO (“Alicyclic/Cyclic 3-Aminoaryl Tertiary 2-Hydroxyalkylamines”) can be acylated to acyl amide compounds of Formula I-WO (“Alicyclic/Cyclic 3-Acylaminoaryl Tertiary 2-Hydroxyalkylamine”).

[0294] Conversion of a 3-amino substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Aminoaryl Tertiary 2-hydroxyalkylamine”) by reaction with carbonyl compounds can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-(Saturated Nitrogen Heterocycl-1yl)aryl Tertiary 2-Hydroxyalkylamine” and “AlicyclictCyclic 3-(Unsaturated Nitrogen Heterocycl-1yl)aryl Tertiary 2-Hydroxyalkylamine”).

[0295] Conversion of a 3-methoxycarbonyl substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Carbomethoxyaryl Tertiary 2-hydroxyalkylamine”) by reaction with amination reagents can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Carboxamidoaryl Tertiary 2-Hydroxyalkylamine”).

[0296] Conversion of a 3-cyano substituent at the R₅ position in Formula I-WO (“Alicyclic/Cyclic 3-Cyanoaryl Tertiary 2-hydroxyalkylamine”) by reaction with organometallic reagents can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Acylaryl Tertiary 2-Hydroxyalkylamine”). Said “Alicyclic/Cyclic 3-Acylaryl Tertiary 2-Hydroxyalkylamines”, can be reduced to hydroxyl compounds of Formula I-WO (“Alicyclic/Cyclic 3-Hydroxysubstitutedmethylaryl Tertiary 2-Hydroxyalkylamine”).

[0297] Conversion of a 3-methoxycarbonyl substituent at the R₁₀ position in Formula I-WO (“Alicyclic/Cyclic 3-Carbomethoxyaryl Tertiary 2-hydroxyalkylamine”) by reaction with amination reagents can afford additional compounds of the present invention of Formula l-WO (“Alicyclic/Cyclic 3-Carboxamidoaryl Tertiary 2-Hydroxyalkylamine”).

[0298] Conversion of a 3-methoxycarbonyl substituent at the R₁₀ position in Formula I-WO (“Alicyclic/Cyclic 3-Carbomethoxyaryl Tertiary 2-hydroxyalkylamine”) by reaction with an organometallic reagent can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-(bis-Organohydroxymethyl)aryl Tertiary 2-Hydroxyalkylamine”).

[0299] Conversion of a 3-methoxycarbonyl substituent at the R₁₀ position in Formula I-WO (“Alicyclic/Cyclic 3-Carbomethoxyaryl Tertiary 2-hydroxyalkylamine”) by reaction with lithium aluminum hydride can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-Hydroxymethylaryl Tertiary 2-Hydroxyalkylamine”).

[0300] Conversion of a 3-methoxycarbonyl substituent at the R₁₀ position in Formula I-WO (“Alicyclic/Cyclic 3-Carbomethoxyaryl Tertiary 2-hydroxyalkylamine”) by reaction with an alkylation reagent can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-(bis-Organo-hydroxymethyl)aryl Tertiary 2-Hydroxyalkylamine”).

[0301] Conversion of a 3-methoxycarbonyl substituent at the R₁₀ position in Formula I-WO (“Alicyclic/Cyclic 3-Carbomethoxyaryl Tertiary 2-hydroxyalkylamine”) by reaction initially with an amidation reagent and then an organometallic reagent can afford additional compounds of the present invention of Formula I-WO (“Alicyclic/Cyclic 3-(Organo-carbonyl)aryl Tertiary 2-Hydroxyalkylamine”).

[0302] Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) and other compounds of this invention posssessing hydroxyl, thiol, and amine functional groups can be converted to a wide variety derivatives. The hydroxyl group X, wherein R₁₆ is a hydrogen, of compounds of the present invention can be readily converted to esters of carboxylic, sulfonic, carbamic, phosphonic, and phosphoric acids. Acylation to form a carboxylic acid ester is readily effected using a suitable acylating reagent such as an aliphatic acid anhydride or acid chloride. The corresponding aryl and heteroaryl acid anhydrides and acid chlorides can also be used. Such reactions are generally carried out using an amine catalyst such as pyridine in an inert solvent. In like manner, compounds that have at least one hydroxyl group present in the form of an alcohol or phenol can be acylated to its corresponding esters. Similarly, carbamic acid esters (urethans) can be obtained by reacting any hydroxyl group with isocyanates and carbamoyl chlorides. Sulfonate, phosphonate, and phosphate esters can be prepared using the corresponding acid chloride and similar reagents. Compounds that have at least one thiol group present can be converted to the corresponding thioesters derivatives analogous to those of alcohols and phenols using the same reagents and comparable reaction conditions. Compounds of Formulas I-WA, I-WO, and other compounds of the present invention that have at least one primary or secondary amine group present can be converted to the corresponding amide derivatives. Amides of carboxylic acids can be prepared using the appropriate acid chloride or anhydrides with reaction conditions analogous to those used with alcohols and phenols. Ureas of the corresponding primary or secondary amine can be prepared using isocyanates directly and carbamoyl chlorides in the presence of an acid scavenger such as triethylamine or pyridine. Sulfonamides can be prepared from the corresponding sulfonyl chloride in the presence of aqueous sodium hydroxide. Suitable procedures and methods for preparing these derivatives can be found in House's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner, Fuson, and Curtin in The Systematic Indentification of Organic Compounds, 5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents for Organic Synthesis, Volume 1, John Wiley & Sons. Reagents of a wide variety that can be used to derivatize hydroxyl, thiol, and amines of compounds of Formulas I-WA, I-WO, and other compounds of the present invention are available from commercial sources or the references cited above, which are incorporated herein by reference.

[0303] Formula I-WO (“Alicyclic/Cyclic Aryl/Heteroaryl Aminoalcohols”) and Formula I-WA (“Alicyclic/Cyclic Aryl/Heteroaryl tertiary Heteroalkylamines”) and other compounds of this invention posssessing hydroxyl, thiol, and amine functional groups can be alkylated to a wide variety derivatives. The hydroxyl group X, wherein R₁₆ is a hydrogen, of compounds of Formulas I-WA, I-WO, and other compounds of the present invention can be readily converted to ethers. Alkylation to form an ether is readily effected using a suitable alkylating reagent such as an alkyl bromide, alkyl iodide or alkyl sulfonate. The corresponding aralkyl, heteroaralkyl, alkoxyalkyl, aralkyloxyalkyl, and heteroaralkyloxyalkyl bromides, iodides, and sulfonates can also be used. Such reactions are generally carried out using an alkoxide forming reagent such as sodium hydride, potassium t-butoxide, sodium amide, lithium amide, and n-butyl lithium using an inert polar solvent such as DMF, DMSO, THF, and similar, comparable solvents. amine catalyst such as pyridine in an inert solvent. In like manner, compounds of Formulas I-WA, I-WO, and the like that have at least one hydroxyl group present in the form of an alcohol or phenol can be alkylated to their corresponding ethers. Compounds of Formulas I-WA, I-WO, and other compounds that have at least one thiol group present can be converted to the corresponding thioether derivatives analogous to those of alcohols and phenols using the same reagents and comparable reaction conditions. Compounds of Formulas I-WA, I-WO, and other compounds that have at least one primary, secondary or tertiary amine group present can be converted to the corresponding quaternary ammonium derivatives. Quaternary ammonium derivatives can be prepared using the appropriate bromides, iodides, and sulfonates analogous to those used with alcohols and phenols. Conditions involve reaction of the amine by warming it with the alkylating reagent with a stoichiometric amount of the amine (i.e., one equivalent with a tertiary amine, two with a secondary, and three with a primary). With primary and secondary amines, two and one equivalents, respectively, of an acid scavenger are used concurrently. Tertiary amines can be prepared from the corresponding primary or secondary amine by reductive alkylation with aldehydes and ketones using reduction methods 1, 2, or 3 as shown in Scheme 1. Suitable procedures and methods for preparing these derivatives can be found in House's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner, Fuson, and Curtin in The Systematic Indentification of Organic Compounds, 5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents for Organic Synthesis, Volume 1, John Wiley & Sons. Perfluoroalkyl derivatives can be prepared as described by DesMarteau in J. Chem. Soc. Chem. Commun. 2241 (1998). Reagents of a wide variety that can be used to derivative hydroxyl, thiol, and amines of compounds of Formulas I-WA, I-WO, and the like are available from commercial sources or the references cited above, which are incorporated herein by reference.

[0304] The following examples are provided to illustrate the present invention and are not intended to limit the scope thereof. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds.

[0305] The following examples are provided to illustrate the present invention and are not intended to limit the scope thereof. Without further elaboration, it is believed that one skilled in the art can, using the preceding descriptions, utilize the present invention to its fullest extent Therefore the following preferred specific embodiments are to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. Compounds containing multiple variations of the structural modifications illustrated in the preceding schemes or the following Examples are also contemplated. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds.

[0306] One skilled in the art may use these generic methods to prepare the following specific examples, which have been or may be properly characterized by ¹H NMR and mass spectrometry. These compounds also may be formed in The following examples contain detailed descriptions of the methods of preparation of compounds of Formula V-H. These detailed descriptions fall within the scope and are presented for illustrative purposes only and are not intended as a restriction on the scope of the invention. All parts are by weight and temperatures are Degrees centigrade unless otherwise indicated.

EXAMPLE 1

[0307]

3-[(4-methylcyclohexyl)[[(3-trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

[0308] EX-1A) 4-Methylcyclohexylamine (1.15 g, 10 mmol, 97%, mixture of cis and trans isomers) and 3-trifluoromethylbenzaldehyde (1.74 g, 10 mmol) were dissolved in anhydrous chloroform (25 mL) and heated under reflux for 4 h using a Dean-Stark trap to remove water. The volatile components were removed in vacuo to give the desired imine (2.69 g) product quantitatively as a colorless oil, MS m/z=269 [M⁺]. The oil was dissolved in methanol, and after cooling to 0° C., solid sodium borohydride was added (0.64 g, 17 mmol). The mixture was allowed to warm to room temperature and stirred for 2 h, then acidified with 1N HCl solution. After neutralizing to pH 7.5 with 2.5N sodium hydroxide, the mixture was extracted with diethyl ether (3×20 mL). The organic layer was washed with brine and water, then dried over anhydrous MgSO₄, and evaporated to give 1.96 g (68.4%) of the desired N-(4-methylcyclohexyl)[[3-(trifluoromethyl)-phenyl] methyl]amine product as a colorless oil, which was greater than 90% pure by reverse phase HPLC analysis. MS m/z=271 [M⁺].

[0309] EX-1B) The benzylamine product from EX-1A (1.08 g, 4 mmol) and 3,3,3-trifluoro-1,2-epoxypropane (0.67 g, 6 mmol) were dissolved in 1.0 mL of acetonitrile. Ytterbium (III) trifluoromethanesulfonate (0.21 g, 0.33 mmol) was added, and the stirred solution was warmed to 50° C. for 2 h under an atmosphere of nitrogen, at which time HPLC analysis indicated that no amine starting material remained. The reaction was quenched with water and extracted with ether. The ether layer was washed with water and brine, then dried over anhydrous MgSO₄. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:12) to give 1.18 g (77%) of the desired 3-[(4-methyl-cyclohexyl)[[(3-trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol product as a light amber oil, 99% pure by HPLC analysis. HRMS calculated for C₁₈H₂₃F₆NO: 384.1762 [M+H]⁺, found: 384.1754. ¹H NMR (CDCl₃) δ0.92 (dd, 3H), 1.17-1.81 (m, 8H), 1.93 (m, 1H), 2.48 (m,1H), 2.80 (m, 2H), 3.76 (d, 2H), 3.79 (m, 1H), 3.94 (s, 1H), 7.45-7.60 (m, 4H). ¹⁹F NMR (CDCl₃) δ−79.2 (d, 3F), −63.1 (s, 3F).

[0310] Additional substituted 3-[(N-alkyl and N-cycloalkyl)[aryl]methyl]amino-1,1,1-trifluoro-2-propanols can be prepared by one skilled in the art using similar methods, as shown in Example Table 1.

Example Table 1. Substituted 3-[(N-alkyl and N-cycloalkyl)[aryl]methyl]amino-1,1,1 -trifluoro-2-propanols.

[0311]

Calculated Observed Ex. Mass Mass No. R_(SUB1) R_(SUB2) [M + H]⁺ [M + H]⁺ 2 cyclopropyl 4-OCF₃ 344.1085 344.1086 3 isopropyl 4-OCF₃ 346.1242 346.1245 4 cyclopropyl 3-OCF₃ 344.1085 344.1085 5 isopropyl 3-OCF₃ 346.1242 346.1239 6 n-propyl 3-OCF₃ 346.1242 346.1252 7 cyclopentyl 3-OCF₃ 372.1398 372.1409

EXAMPLE 8

[0312]

3-[(3-methyl-2-butenyl)[(3-(trifluoromethoxy)phenyl] amino]-1,1,1-trifluoro-2-propanol

[0313] EX8A) 3-Trifluoromethoxy aniline (23.81 g, 134.4 mmol) and 3,3,3-trifluoro-1,2-epoxypropane (3.76 g, 33.6 mmol) were placed into a sealed tube and heated at 80° C. for 24 h. The excess aniline was removed by distillation (70° C. at 80 torr). The resulting residue contained 8.6 g (>95%) of the desired 3-[ [(trifluoromethoxy)phenyl]-amino]-1,1,1-trifluoro-2-propanol product as a light yellow oil. ¹H NMR (CDCl₃) δ3.29-3.37 (m, 1H), 3.55 (dd, 1H), 4.20 (m, 1H), 6.48-6.63 (m, 3H), 7.12 (t, 1H). ¹⁹F NMR (CDCl₃) δ−79.36 (s, 3F), −58.44 (s, 3F).

[0314] EX-8B) The 3-[[(trifluoromethoxy)phenyl]amino]-1,1,1-trifuoro-2-propanol product from EX8A (18.68 g, 64.6 mmol) and imidazole (10.99 g, 0.162 mmol) were dissolved in dimethylfornamide (40.0 mL) and t-butyldimethylsilylchloride (11.69 g, 77.6 mmol) was added in 3.0 g portions over 15 min. The reaction was stirred at 23° C. for 18 h. The resulting solution was diluted with ethyl acetate and washed with water and brine. The organic layer was dried (MgSO₄) and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with 25% ethyl acetate in hexane to afford 17.08 g of the desired silylated product as a light golden oil. FABMS m/z= 404 [M+H]⁺. ¹H NMR (CDCl₃) δ 0.042 (s, 3H), 0.085 (s, 3H), 0.91 (s, 9H), 3.25-3.35 (m, 1H), 3.50 (dd, 1H), 4.10 (m, 1H), 6.40 (bs, 1H), 6.50 (dd, 1H), 6.59 (d, 1H), 7.17 (t, 1H).

[0315] EX-8C) The silylated product from EX8B (0.15 g, 0.372 mmol ) was dissolved in THF (0.5 mL) in a 2-dram glass vial with stir bar and cooled to 0° C. in an ice bath. KOtBu (1M in THF, 1.2 eq, 0.446 mmol, 0.446 mL) was added to the cold solution in one portion. The reaction mixture was stirred at 0° C. for 5 min, then 1-chloro-3-methyl-2-butene (38.9 mg, 0.372 mmol) in 0.5 mL of THF was added in one portion to the cold reaction mixture. The ice bath was removed, and the reaction was stirred at 23° C. for 18 h. The resulting solution was diluted with ethyl acetate and washed with water and brine. The organic layer was dried (MgSO₄) and concentrated under a nitrogen stream. The crude residue was dissolved in 2.0 mL of THF and treated with tetrabutylammonium fluoride (1M in THF, 1.2 eq, 0.446 mmol, 0.446 mL). The reaction mixture was stirred at 23° C. for 3 h. The reaction was diluted with ethyl acetate and washed with water and brine. The organic layer wad dried (MgSO₄) and concentrated under a nitrogen stream. The crude residue was purified using 0.5 g of silica gel eluting with hexane (100%) followed by 30% ethyl acetate in hexane to give 59.1 mg (44.4% yield) of the desired 3-[(3-methyl-2-butenyl)[(3-(trifluoromethoxy)-phenyl] amino]-1,1,1-trifluoro-2-propanol product as a golden oil. FABMS m/z= 358 [M+H]⁺.

[0316] Additional examples of substituted 3-[(N-alkyl, N-alkenyl and N-alkynyl)-[ (trifluoromethoxy)phenyl] amino]-1,1,1-trifluoro-2-propanols can be prepared by one skilled in the art using similar methods, as shown in Example Table 2.

Example Table 2. 3-[(N-alkyl, N-alkenyl and N-alkynyl)[(trifluoromethoxy)phenyl]amino]-1,1,1 -trifluoro-2-propanols.

[0317]

Ex. Calculated Observed No. R_(SUB1) Mol. Wt. Mass [M + H]⁺  9 2,3-octenyl 399 400 10 2,3-propynyl 327 328 11 3-methyl-butyl 359 360 12 2-(carbomethoxy)-2-pro- 387 388 penyl 13 3-(carbomethoxy)-2-pro- 387 388 penyl 15 4-methoxy-2-butenyl 373 374

EXAMPLE 15

[0318]

1,1′-[(Phenylmethyl)imino]bis[3,3,3-trifluoro-2-propanol]

[0319] Benzylamine (1.5 eq, 2.88 g, 2.94 mL, 26.8 mmol) was combined with 3,3,3-trifluoro-1,2-epoxypropane (2.0 g, 17.86 mmol) in a sealed glass tube and heated at 80° C. for 18 h. Upon cooling to room temperature, the reaction mixture formed a slushy white solid. The solid was collected by filtration and washed with diethyl ether. The mother liquor was concentrated in vacuo to give 1.71 g (43%) of the desired 1,1′-[(phenyl-methyl)imino]bis[3,3,3-trifluoro-2-propanol] product as a colorless oil. FABMS m/z=332 [M+H]⁺. ¹H NMR (CDCl₃) δ 2.85-2.96 (m, 4H), 3.94 (s, 2H), 3.94-3.97 (m, 2H), 7.24- 7.37 (m, 5H).

[0320] Additional examples of substituted 1,1′-[(phenylmethyl)imino]bis[3,3,3-tri-fluoro-2-propanols] can be prepared by one skilled in the art using similar methods, as shown in Example Table 3.

Example Table 3. Substituted 1,1′-[(phenylmethyl)imino]bis[3,3,3-trifluoro-2-propanols]

[0321]

Ex. Calculated Observed Mass No. R_(SUB2) Mass [M + H]⁺ [M + H]⁺ 16 3-trifluoromethyl 400.0959 400.0923 17 4-trifluoromethoxy 416.0908 416.0905

EXAMPLE 18

[0322]

3-[[3-(4-chloro-3-ethylphenoxy)phenyl][3-cyclohexylmethyl]amino]-1,1,1-trifluoro-2-propanol

[0323] EX-18A) To a solution of 1,3-dinitrobenzene (16.8 g, 0.1 mol) and 4-chloro-3-ethylphenol (15.6 g, 0.1 mol) in 200 mL of dimethylsulfoxide was added cesium carbonate (65 g, 0.2 mol). The reaction mixture was heated at 100° C. under nitrogen overnight then cooled to room temperature. The reaction mixture was filtered through celite then rinsed with diethyl ether and a small amount of water. The filtrate was extracted several times with diethyl ether. The organic layers were combined, washed with water and brine, dried over MgSO₄, and concentrated in vacuo to give 21.8 g (78%) of the desired 3-(4-chloro-3-ethylphenoxy)-1-nitrobenzene product as a dark orange oil, which was greater than 90% pure by reverse phase HPLC analysis. HRMS calcd. for C₁₄H ₁₂ClNO₃: 295.0849 [M+NH₄]⁺, found 295.0862.

[0324] EX-18B) To a solution of 3-(4-chloro-3-ethylphenoxy)-1-nitrobenzene (10 g, 0.036 mol) from EX-18A in 400 mL of glacial acetic acid and 1 mL of water was added zinc metal (20 g, 0.305 mol) at room temperature, and the resultant mixture was stirred for 1 h. The reaction mixture was filtered through celite. The filtrate was neutralized with ammonium hydroxide and extracted with diethyl ether. The organic layer was washed with water and brine, dried over MgSO₄, and concentrated in vacuo to give 10 g (100%) of the desired 3-(4-chloro-3-ethylphenoxy)aniline product as a dark orange oil, which was greater than 90% pure by reverse phase HPLC analysis. HRMS calcd. for C₁₄H₁₄ClNO: 248.0842 [M+H]⁺, found: 248.0833.

[0325] EX-18C) The 3-(4-chloro-3-ethylphenoxy)aniline (0.545 g, 0.002 mol) product from EX-18B was mixed with neat 3,3,3-trifluoro-1,2-epoxypropane (0.220 g, 0.002 mol) in a pressurized vial. The resulting mixture was heated at 90° C. for 18 h, cooled, and the excess 3,3,3-trifluoro-1,2-epoxypropane was removed in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane to give 0.254 g (35%) of the desired 3-[[3-(4-chloro-3-ethyl-phenoxy)phenyl]amino]-1,1,1-trifluoro-2-propanol product as a pure orange oil. Anal calcd. for C₁₇H₁₇NOF₃Cl: C, 56.75; H, 4.76; N, 3.89. Found: C, 56.72; H, 4.70; N, 3.85. HRMS calcd.: 360.0978 [M+H], found: 360.0969. H NMR (CDCl₃) δ 1.50 (t, 3H), 2.72 (m, 2H), 3.36 (m, 1H), 3.54 (m, 1H), 4.20 (m, 1H), 6.42 (m, 2H), 6.81 (dd, 1H), 6.94 (d, 1H), 7.18 (d, 1H), 7.25 (m, 2H).

[0326] The 3-[[3-(4-chloro-3-ethylphenoxy)phenyl]amino]-1,1,1 -trifluoro-2-propanol product from EX-18C was dissolved in 12 mL of tetrahydrofuran. To this stirred solution was added cyclohexanecarboxaldehyde (0.032 g, 0.285 mmol), followed by sodium tri-acetoxyborohydride (0.079 g, 0.370 mmol and concentrated acetic acid (0.020 g, 0.325 mmol). The resulting mixture was stirred at room temperature for 18 h. Additional cyclohexanecarboxaldehyde (0.032 g, 0.285 mmol) was added and the mixture was allowed to stir at room temperature for another 18 h. The reaction was quenched with saturated sodium bicarbonate and extracted with methylene chloride. The organic layers were combined, dried over MgSO₄ and concentrated to an orange/brown oil. The crude product was purified by flash column chromatography on silica gel eluting with 1:4 ethyl acetate in hexane to give 0.080 g (61%) of the desired 3-[[3-(4-chloro-3-ethylphenoxy)phenyl] [3 -cyclohexylmethyl]amino]-1,1,1 -trifluoro-2-propanol product as a yellow-orange oil (>95% pure by HPLC). HRMS calcd.: 456.1917 [M+H]⁺, found: 456.1942. ¹H NMR (CDCl₃) δ 0.82-1.01 (m, 2H), 1.22-1.27 (m, 3H), 1.73-1.76 (m, 5H), 2.74 (dd, 2H), 3.15 (dd, 2H), 3.23 (dd, 1H), 3.52 (m, 1H), 3.80 (dd, 1H), 4.28 (m, 1H), 6.34 (d, 2H), 6.42 (d, 1H), 6.83 (dd, 1H), 6.98 (d, 1H), 7.19 (t, 1H), 7.29 (d, 1H). ¹⁹F NMR (CDCl₃) δ −79.06 (d, 3F).

[0327] Based on the preceding procedures, additional substituted 3-[(N-alkyl)-[ [aryl]methyl]amino]-1,1,1-trifluoro-2-propanols and 3-[(N-cycloalkyl)-[ [aryl]methyl]-amino]-halo-2-propanols are prepared by one skilled in the art using similar methods, as shown in Example Tables 4 and 5. Similarly, substituted 3-[ (N-aryl)[[cycloalkyl]-methyl]amino]-halo-2-propanols and substituted 3-[(N-aryl)[ [haloalkyl]methyl]amino]-halo-2-propanols are prepared by one skilled in the art using analogous methods, as shown in Example Tables 6 and 7.

Example Table 4. 3-[(N-alkyl)[[aryl]methyl]amino]- 1,1,1 -trifluoro-2-propanols.

[0328] Ex. No. R_(SUB)

 19 4-OCF₃  20 3-OCF₂CF₂H  21 2-F, 5-CF₃  22 2-F, 4-CF₃  23 3-CF₃, 4-F  24 3-CF₃CF₂  25 3-cyclopentyl  26 3-isopropoxy  27 3-SCF₃  28 3-sec-butoxy  29 3-C(CF₃)₂OH  30 3-(2-furyl)  31 3-(3-furyl)  32 3-isobutyl  33 3-isobutoxy  34 3-ethoxy  35 3-OCH₂CF₃  36 3-propoxy  37 3-tert-butoxy  38 3-(2-thienyl)  39 3-cyclopropyl  40 4-F, 3-(2-furyl)  41 3-(3-CF₃-phenoxy)  42 3,4-(OCF₂CF₂O)  43 3-OCF₂CF₃  44 3-cyclopentoxy  45 3-(cyclopropyl)methoxy  46 3-OCH₂CH(OH)CF₃  47 3-CF₃  48 4-CF₃  49 3-CH₂CF₂CF₃  50 3-CH₂CF₃  51 3-CH(CF₃)₂  52 3-CF₂CF₂CF₃  53 3-phenoxy  54 3-phenyl  55 3-(tetrahydro-2-furyl)  56 isoamyl

 57 3-OCF₃  58 3-OCF₂CF₂H  59 2-F, 5-CF₃  60 2-F, 4-CF₃  61 3-CF₃, 4-F  62 3-CF₃CF₂  63 3-cyclopentyl  64 3-isopropoxy  65 3-SCF₃  66 3-sec-butoxy  67 3-C(CF₃)₂OH  68 3-(2-furyl)  69 3-(3-furyl)  70 3-isobutyl  71 3-isobutoxy  72 3-ethoxy  73 3-OCH₂CF₃  74 3-propoxy  75 3-tert-butoxy  76 3-(2-thienyl)  77 3-cyclopropyl  78 4-F, 3-(2-furyl)  79 3-(3-CF₃-phenoxy)  80 3,4-(OCF₂CF₂O)  81 3-OCF₂CF₃  82 3-cyclopentoxy  83 3-(cyclopropyl)methoxy  84 3-OCH₂CH(OH)CF₃  85 3-CF₃  86 4-CF₃  87 3-CH₂CF₂CF₃  88 3-CH₂CF₃  89 3-CH(CF₃)₂  90 3-CF₂CF₂CF₃  91 3-phenoxy  92 3-phenyl  93 3-(tetrahydro-2-furyl)  94 isoamyl

 95 3-OCF₃  96 3-OCF₂CF₂H  97 2-F, 5-CF₃  98 2-F, 4-CF₃  99 3-CF₃, 4-F 100 3-CF₃CF₂ 101 3-cyclopntyl 102 3-isopropoxy 103 3-SCF₃ 104 3-sec-butoxy 105 3-C(CF₃)₂OH 106 3-(2-furyl) 107 3-(3-furyl) 108 3-isobutyl 109 3-isobutoxy 110 3-ethoxy 111 3-OCH₂CF₃ 112 3-propoxy 113 3-tert-butoxy 114 3-(2-thienyl) 115 3-cyclopropyl 116 4-F, 3-(2-furyl) 117 3-(3-CF₃-phenoxy) 118 3,4-(OCF₂CF₂O) 119 3-OCF₂CF₃ 120 3-cyclopentoxy 121 3-(cyclopropyl)methoxy 122 3-OCH₂CH(OH)CF₃ 123 3-CF₃ 124 4-CF₃ 125 3-CH₂CF₂CF₃ 126 3-CH₂CF₃ 127 3-CH(CF₃)₂ 128 3-CF₂CF₂CF₃ 129 3-phenoxy 130 3-phenyl 131 3-(tetrahydro-2-furyl) 132 isoamyl

133 3-OCF₃ 134 3-OCF₂CF₂H 135 2-F, 5-CF₃ 136 2-F, 4-CF₃ 137 3-CF₃, 4-F 138 3-CF₃CF₂ 139 3-cyclopentyl 140 3-isopropoxy 141 3-SCF₃ 142 3-sec-butoxy 143 3-C(CF₃)₂OH 144 3-(2-furyl) 145 3-(3-furyl) 146 3-isobutyl 147 3-isobutoxy 148 3-ethoxy 149 3-OCH₂CF₃ 150 3-propoxy 151 3-tert-butoxy 152 3-(2-thienyl) 153 3-cyclopropyl 154 4-F, 3-(2-furyl) 155 3-(3-CF₃-phenoxy) 156 3,4-(OCF₂CF₂O) 157 3-OCF₂CF₃ 158 3-cyclopentoxy 159 3-(cyclopropyl)methoxy 160 3-OCH₂CH(OH)CF₃ 161 3-CF₃ 162 4-CF₃ 163 3-CH₂CF₂CF₃ 164 3-CH₂CF₃ 165 3-CH(CF₃)₂ 166 3-CF₂CF₂CF₃ 167 3-phenoxy 168 3-phenyl 169 3-(tetrahydro-2-furyl) 170 isoamyl

171 3-OCF₃ 172 3-OCF₂CF₂H 173 2-F, 5-CF₃ 174 2-F, 4-CF₃ 175 3-CF₃, 4-F 176 3-CF₃CF₂ 177 3-cyclopentyl 178 3-isopropoxy 179 3-SCF₃ 180 3-sec-butoxy 181 3-C(CF₃)₂OH 182 3-(2-furyl) 183 3-(3-furyl) 184 3-isobutyl 185 3-isobutoxy 186 3-ethoxy 187 3-OCH₂CF₃ 188 3-propoxy 189 3-tert-butyoxy 190 3-(2-thienyl) 191 3-cyclopropyl 192 4-F, 3-(2-furyl) 193 3-(3-CF₃-phenoxy) 194 3,4-(OCF₂CF₂O) 195 3-OCF₂CF₃ 196 3-cyclopenoxy 197 3-(cyclopropyl)methoxy 198 3-OCH₂CH(OH)CF₃ 199 3-CF₃ 200 4-CF₃ 201 3-CH₂CF₂CF₃ 202 3-CH₂CF₃ 203 3-CH(CF₃)₂ 204 3-CF₂CF₂CF₃ 205 3-phenoxy 206 3-phenyl 207 3-(tetrahydro-2-furyl) 208 isoamyl

Example Table 5. (cont.). 3-[(N-cycloalkyl)[[aryl]methyl]amino]-halo-2-propanols.

[0329] Ex. No. R_(SUB)

209 3-tert-butoxy 210 3-OCF₂CF₂H 211 2-F, 5-CF₃ 212 2-F, 4-CF₃ 213 3-CF₃, 4-F 214 3-CF₃CF₂ 215 3-cyclopentyl 216 3-isopropoxy 217 3-SCF₃ 218 3-sec-butoxy 219 3-C(CF₃)₂OH 220 3-(2-furyl) 221 3-(3-furyl) 223 3-isobutoxy 224 3-ethoxy 225 3-OCH₂CF₃ 226 3-propoxy 227 3-(2-pyridyl) 228 3-(2-thienyl) 229 3-cyclopropyl 230 4-F, 3-(2-furyl) 231 3-(3-CF₃-phenoxy) 232 3,4-(OCF₂CF₂O) 233 3-OCF₂CF₃ 234 3-cyclopentoxy 235 3-(cyclopropyl)methoxy 236 3-OCH₂CH(OH)CF₃ 237 3-CF₃ 238 4-CF₃ 239 3-CH₂CF₂CF₃ 240 3-CH₂CF₃ 241 3-CH(CF₃)₂ 242 3-CF₂CF₂CF₃ 243 3-phenoxy 244 3-phenyl 245 3-(tetrahydro-2-furyl) 246 isoamyl

247 4-OCF₃ 248 3-OCF₂CF₂H 249 2-F, 5-CF₃ 250 2-F, 4-CF₃ 251 3-CF₃CF₂ 252 3-CF₃CF₂ 253 3-cyclopentyl 254 3-isopropoxy 255 3-SCF₃ 256 3-sec-butoxy 257 3-C(CF₃)₂OH 258 3-(2-furyl) 259 3-(3-furyl) 260 3-isobutyl 261 3-isobutoxy 262 3-ethoxy 263 3-OCH₂CF₃ 264 3-propoxy 265 3-tert-butoxy 266 3-(2-thienyl) 267 3-cyclopropyl 268 4-F, 3-(2-furyl) 269 3-(3-CF₃-phenoxy) 270 3,4-(OCF₂CF₂O) 271 3-OCF₂CF₃ 272 3-cyclopentoxy 273 3-(cyclopropyl)methoxy 274 3-OCH₂CH(OH)CF₃ 275 3-CF₃ 276 4-CF₃ 277 3-CH₂CF₂CF₃ 278 3-CH₂CF₃ 279 3-CH(CF₃)₂ 280 3-CF₂CF₂CF₃ 281 3-phenoxy 282 3-phenyl 283 3-(tetrahydro-2-furyl) 284 isoamyl

285 3-OCF₃ 286 3-OCF₂CF₂H 287 2-F, 5-CF₃ 288 2-F, 4-CF₃ 289 3-CF₃, 4-F 290 3-CF₃CF₂ 291 3-cyclopentyl 292 3-isopropoxy 293 3-SCF₃ 294 3-sec-butoxy 295 3-C(CF₃)₂OH 296 3-(2-furyl) 297 3-(3-furyl) 298 3-isobutyl 299 3-isobutyl 300 3-ethoxy 301 3-OCH₂CF₃ 302 3-propoxy 303 3-tert-butoxy 304 3-(2-thienyl) 305 3-cyclopropyl 306 4-F, 3-(2-furyl) 307 3-(3-CF₃-phenoxy) 308 3,4-(OCF₂CF₂O) 309 3-OCF₂CF₃ 310 3-cyclopentoxy 311 3-(cyclopropyl)methoxy 312 3-OCH₂CH(OH)CF₃ 313 3-CF₃ 314 4-CF₃ 315 3-CH₂CF₂CF₃ 316 3-CH₂CF₃ 317 3-CH(CF₃)₂ 318 3-CF₂CF₂CF₃ 319 3-phenoxy 320 3-phenyl 321 3-(tetrahydro-2-furyl) 322 isoamyl

324 3-OCF₃ 324 3-OCF₂CF₂H 325 2-F, 5-CF₃ 326 2-F, 4-CF₃ 327 3-CF₃, 4-F 328 3-CF₃CF₂ 329 3-cyclopentyl 330 3-isopropoxy 331 3-SCF₃ 332 3-sec-butoxy 333 3-C(CF₃)₂OH 334 3-(2-furyl) 335 3-(3-furyl) 336 3-isobutyl 337 3-isobutoxy 338 3-ethoxy 339 3-OCH₂CF₃ 340 3-propoxy 341 3-tert-butoxy 342 3-(2-thienyl) 343 3-cyclopropyl 344 4-F, 3-(2-furyl) 345 3-(3-CF₃-phenoxy) 346 3,4-(OCF₂CF₂O) 347 3-OCF₂CF₃ 348 3-cyclopentoxy 349 3-(cyclopropyl)methoxy 350 3-OCH₂CH(OH)CF₃ 351 3-CF₃ 352 4-CF₃ 353 3-CH₂CF₂CF₃ 354 3-CH₂CF₃ 355 3-CH(CF₃)₂ 356 3-CF₂CF₂CF₃ 357 3-phenoxy 358 3-phenyl 359 3-(tetrahydro-2-furyl) 360 isoamyl

361 3-OCF₃ 362 3-OCF₂CF₂H 363 2-F, 5-CF₃ 364 2-F, 4-CF₃ 365 3-OCF₃, 4-F 366 3-CF₃CF₂ 367 3-cyclopentyl 368 3-isopropoxy 369 3-SCF₃ 370 3-sec-butoxy 371 3-C(CF₃)₂OH 372 3-(2-furyl) 373 3-(3-furyl) 374 3-isobutyl 375 3-isobutoxy 376 3-ethoxy 377 3-OCH₂CF₃ 378 3-propoxy 379 3-tert-butoxy 380 3-(2-thienyl) 381 3-cyclopropyl 382 4-F, 3-(2-furyl) 383 3-(3-CF₃phenoxy) 384 3,4-OCF₂CF₂O) 385 3-OCF₂CF₃ 386 3-cyclopentoxy 387 3-(cyclopropyl)methoxy 388 3-OCH₂CH(OH)CF₃ 389 3-CF₃ 390 4-CF₃ 391 3-CH₂CF₂CF₃ 392 3-CH₂CF₃ 393 3-CH(CF₃)₂ 394 3-CF₂CF₂CF₃ 395 3-phenoxy 396 3-phenyl 397 3-(tetrahydro-2-furyl) 398 isoamyl

399 3-OCF₃ 400 3-OCF₂CF₂H 401 2-F, 5-CF₃ 402 2-F, 4-CF₃ 403 3-CF₃, 4-F 404 3-CF₃CF₂ 405 3-cyclopentyl 406 3-isopropoxy 407 3-SCF₃ 408 3-sec-butoxy 409 3-C(CF₃)₂OH 410 3-(2-furyl) 411 3-(3-furyl) 412 3-isobutyl 413 3-isobutoxy 414 3-ethoxy 415 3-OCH₂CF₃ 416 3-propoxy 417 3-tert-butoxy 418 3-(2-thienyl) 419 3-cyclopropyl 420 4-F, 3-(2-furyl) 421 3-(3-CF₃-phenoxy) 422 3,4-(OCF₂CF₂O) 423 3-OCF₂CF₃ 424 3-cyclopentoxy 425 3-(cyclopropyl)methoxy 426 3-OCH₂CH(OH)CF₃ 427 3-CF₃ 428 4-CF₃ 429 3-CH₂CF₂CF₃ 430 3-CH₂CF₃ 431 3-CH(CF₃)₂ 432 3-CF₂CF₂CF₃ 433 3-phenoxy 434 3-phenyl 435 3-(tetrahydro-2-furyl) 436 isoamyl

437 3-OCF₃ 438 3-OCF₂CF₂H 439 2-F, 5-CF₃ 440 2-F, 4-CF₃ 441 3-CF₃, 4-F 442 3-CF₃CF₂ 443 3-cyclopentyl 444 3-isopropoxy 445 3-SCF₃ 446 3-sec-butoxy 447 3-C(CF₃)₂OH 448 3-(2-furyl) 449 3-(3-furyl) 450 3-isobutyl 451 3-isobutoxy 452 3-ethoxy 453 3-OCH₂CF₃ 454 3-propoxy 455 3-tert-butoxy 456 3-(2-thienyl) 457 3-cyclopropyl 458 4-F, 3-(2-furyl) 459 3-(3-CF₃-phenoxy) 460 3,4-(OCF₂CF₂O) 461 3-OCF₂CF₃ 462 3-cyclopentoxy 463 3-(cyclopropyl)methoxy 464 3-OCH₂CH(OH)CF₃ 465 3-CF₃ 466 4-CF₃ 467 3-CH₂CF₂CF₃ 468 3-CH₂CF₃ 469 3-CH(CF₃)₂ 470 3-CF₂CF₂CF₃ 471 3-phenoxy 472 3-phenyl 473 3-(tetrahydro-2-furyl) 474 isoamyl

475 3-OCF₃ 476 3-OCF₂CF₂H 477 2-F, 5-CF₃ 478 2-F, 4-CF₃ 479 3-CF₃, 4-F 480 3-CF₃CF₂ 481 3-cyclopentyl 482 3-isopropoxy 483 3-SCF₃ 484 3-sec-butoxy 485 3-C(CF₃)₂OH 486 3-(2-furyl) 487 3-(3-furyl) 488 3-isobutyl 489 3-isobutoxy 490 3-ethoxy 491 3-OCH₂CF₃ 492 3-propoxy 493 3-tert-butoxy 494 3-(2-thienyl) 495 3-cyclopropyl 496 4-F, 3-(2-furyl) 497 3-(3-CF₃-phenoxy) 498 3,4-(OCF₂CF₂O) 499 3-OCF₂CF₃ 500 3-cyclopentoxy 501 3-(cyclopropyl)methoxy 502 3-OCH₂CH(OH)CF₃ 503 3-CF₃ 504 4-CF₃ 505 3-CH₂CF₂CF₃ 506 3-CH₂CF₃ 507 3-CH(CF₃)₂ 508 3-CF₂CF₂CF₃ 509 3-phenoxy 510 3-phenyl 511 3-(tetrahydro-2-furyl) 512 isoamyl

513 3-OCF₃ 514 3-OCF₂CF₂H 515 2-F, 5-CF₃ 516 2-F, 4-CF₃ 517 3-CF₃, 4-F 518 3-CF₃CF₂ 519 3-cyclopentyl 520 3-isopropoxy 521 3-SCF₃ 522 3-sec-butoxy 523 3-C(CF₃)₂OH 524 3-(2-furyl) 525 3-(3-furyl) 526 3-isobutyl 527 3-isobutoxy 528 3-ethoxy 529 3-OCH₂CF₃ 530 3-propoxy 531 3-tert-butoxy 532 3-(2-thienyl) 533 3-cyclopropyl 534 4-F, 3-(2-furyl) 535 3-(3-CF₃-phenoxy) 536 3,4-(OCF₂CF₂O) 537 3-OCF₂CF₃ 538 3-cyclopentoxy 539 3-(cyclopropyl)methoxy 540 3-OCH₂CH(OH)CF₃ 541 3-CF₃ 542 4-CF₃ 543 3-CH₂CF₂CF₃ 544 3-CH₂CF₃ 545 3-CH(CF₃)₂ 546 3-CF₂CF₂CF₃ 547 3-phenoxy 548 3-phenyl 549 3-(tetrahydro-2-furyl) 550 isoamyl

551 3-OCF₃ 552 3-OCF₂CF₂H 553 2-F, 5-CF₃ 554 2-F, 4-CF₃ 555 3-CF₃, 4-F 556 3-CF₃CF₂ 557 3-cyclopentyl 558 3-isopropoxy 559 3-SCF₃ 560 3-sec-butoxy 561 3-C(CF₃)₂OH 562 3-(2-furyl) 563 3-(3-furyl) 564 3-isobutyl 565 3-isobutoxy 566 3-ethoxy 567 3-OCH₂CF₃ 568 3-propoxy 569 3-tert-butoxy 570 3-(2-thienyl) 571 3-cyclopropyl 572 4-F, 3-(2-furyl) 573 3-(3-CF₃phenoxy) 574 3,4-(OCF₂CF₂O) 575 3-OCF₂CF₃ 576 3-cyclopentyl 577 3-(cyclopropyl)methoxy 578 3-OCH₂CH(OH)CF₃ 579 3-CF₃ 580 4-CF₃ 581 3-CH₂CF₂CF₃ 582 3-CH₂CF₃ 583 3-CH(CF₃)₂ 584 3-CF₂CF₂CF₃ 585 3-phenoxy 586 3-phenyl 587 3-(tetrahydro-2-furyl) 588 isoamyl

589 3-OCF₃ 590 3-OCF₂CF₂H 591 2-F, 5-CF₃ 592 2-F, 4-CF₃ 593 3-CF₃, 4-F 594 3-CF₃CF₂ 595 3-cyclopentyl 596 3-isopropoxy 597 3-SCF₃ 598 3-sec-butoxy 599 3-C(CF₃)₂OH 600 3-(2-furyl) 601 3-(3-furyl) 602 3-isobutyl 603 3-isobutoxy 604 3-ethoxy 605 3-OCH₂CF₃ 606 3-propoxy 607 3-tert-butoxy 608 3-(2-thienyl) 609 3-cyclopropyl 610 4-F, 3-(2-furyl) 611 3-(3-CF₃-phenoxy) 612 3,4-(OCF₂CF₂O) 613 3-OCF₂CF₃ 614 3-cyclopentoxy 615 3-(cyclopropyl)methoxy 616 3-OCH₂CH(OH)CF₃ 617 3-CF₃ 618 4-CF₃ 619 3-CH₂CF₂CF₃ 620 3-CH₂CF₃ 621 3-CH(CF₃)₂ 622 3-CF₂CF₂CF₃ 623 3-phenoxy 624 3-phenyl 625 3-(tetrahydro-2-furyl) 626 isoamyl

627 3-OCF₃ 628 3-OCF₂CF₂H 629 2-F, 5-CF₃ 630 2-F, 4-CF₃ 631 3-CF₃, 4-F 632 3-CF₃CF₂ 633 3-cyclopentyl 634 3-isopropoxy 635 3-SCF₃ 636 3-sec-butoxy 637 3-C(CF₃)₂OH 638 3-(2-furyl) 639 3-(3-furyl) 640 3-isobutyl 641 3-isobutoxy 642 3-ethoxy 643 3-OCH₂CF₃ 644 3-propoxy 645 3-tert-butoxy 646 3-(2-thienyl) 647 3-cyclopropyl 648 4-F, 3-(2-furyl) 649 3-(3-CF₃-phenoxy) 650 3,4-(OCF₂CF₂O) 651 3-OCF₂CF₃ 652 3-cyclopentoxy 653 3-(cyclopropyl)methoxy 654 3-OCH₂CH(OH)CF₃ 655 3-CF₃ 656 4-CF₃ 657 3-CH₂CF₂CF₃ 658 3-CH₂CF₃ 659 3-CH(CF₃)₂ 660 3-CF₂CF₂CF₃ 661 3-phenoxy 662 3-phenyl 663 3-(tetrahydro-2-furyl) 664 isoamyl

665 3-OCF₃ 666 3-OCF₂CF₂H 667 2-F, 5-CF₃ 668 2-F, 4-CF₃ 669 3-CF₃, 4-F 670 3-CF₃CF₂ 671 3-cyclopentyl 672 3-isopropoxy 673 3-SCF₃ 674 3-sec-butoxy 675 3-C(CF₃)₂OH 676 3-(2-furyl) 677 3-(3-furyl) 678 3-isobutyl 679 3-isobutoxy 680 3-ethoxy 681 3-OCH₂CF₃ 682 3-propoxy 683 3-tert-butoxy 684 3-(2-thienyl) 685 3-cyclopropyl 686 4-F, 3-(2-furyl) 687 3-(3-CF₃-phenoxy) 688 3,4-(OCF₂CF₂O) 689 3-OCF₂CF₃ 690 3-cyclopentoxy 691 3-(cyclopropyl)methoxy 692 3-OCH₂CH(OH)CF₃ 693 3-CF₃ 694 4-CF₃ 695 3-CH₂CF₂CF₃ 696 3-CH₂CF₃ 697 3-CH(CF₃)₂ 698 3-CF₂CF₂CF₃ 699 3-phenoxy 700 3-phenyl 701 3-(tetrahydro-2-furyl) 702 isoamyl

703 3-OCF₃ 704 3-OCF₂CF₂H 705 2-F, 5-CF₃ 706 2-F, 4-CF₃ 707 3-CF₃, 4-F 708 3-CF₃CF₂ 709 3-cyclopentyl 710 3-isopropoxy 711 3-SCF₃ 712 3-sec-butoxy 713 3-C(CF₃)₂OH 714 3-(2-furyl) 715 3-(3-furyl) 716 3-isobutyl 717 3-isobutoxy 718 3-ethoxy 719 3-OCH₂CF₃ 720 3-propoxy 721 3-tert-butoxy 722 3-(2-thienyl) 723 3-cyclopropyl 724 4-F, 3-(2-furyl) 725 3-(3-CF₃-phenoxy) 726 3,4-(OCF₂CF₂O) 727 3-OCF₂CF₃ 728 3-cyclopentyl 729 3-(cyclopropyl)methoxy 730 3-OCH₂CH(OH)CF₃ 731 3-CF₃ 732 4-CF₃ 733 3-CH₂CF₂CF₃ 734 3-CH₂CF₃ 735 3-CH(CF₃)₂ 736 3-CF₂CF₂CF₃ 737 3-phenoxy 738 3-phenyl 739 3-(tetrahydro-2-furyl) 740 isoamyl

741 3-OCF₃ 742 3-OCF₂CF₂H 743 2-F, 5-CF₃ 744 2-F, 4-CF₃ 745 3-CF₃, 4-F 746 3-CF₃CF₂ 747 3-cyclopentyl 748 30isopropoxy 749 3-SCF₃ 750 3-sec-butoxy 751 3-C(CF₃)₂OH 752 3-(2-furyl) 753 3-(3-furyl) 754 3-isobutyl 755 3-isobutoxy 756 3-ethoxy 757 3-OCH₂CF₃ 758 3-propoxy 759 3-tert-butoxy 760 3-(2-thienyl) 761 3-cyclopropyl 762 4-F, 3-(2-furyl) 763 3-(3-CF₃-phenoxy) 764 3,4-(OCF₂CF₂O) 765 3-OCF₂CF₃ 766 3-cyclopentyl 767 3-(cyclopropyl)methoxy 768 3-OCH₂CH(OH)CF₃ 769 3-CF₃ 770 4-CF₃ 771 3-CH₂CF₂CF₃ 772 3-CH₂CF₃ 773 3-CH(CF₃)₂ 774 3-CF₂CF₂CF₃ 775 3-phenoxy 776 3-phenyl 777 3-(tetrahydro-2-furyl) 778 isoamyl

779 3-OCF₃ 780 3-OCF₂CF₂H 781 2-F, 5-CF₃ 782 2-F, 4-CF₃ 783 3-CF₃, 4-F 784 3-CF₃CF₂ 785 3-cyclopentyl 786 3-isopropoxy 787 3-SCF₃ 788 3-sec-butoxy 789 3-C(CF₃)₂OH 790 3-(2-furyl) 791 3-(3-furyl) 792 3-isobutyl 793 3-isobutoxy 794 3-ethoxy 795 3-OCH₂CF₃ 796 3-propoxy 797 3-tert-butoxy 798 3-(2-thienyl) 799 3-cyclopropyl 800 4-F, 3-(2-furyl) 801 3-(3-CF₃-phenoxy) 802 3,4-(OCF₂CF₂O) 803 3-OCF₂CF₃ 804 3-cyclopentyl 805 3-(cyclopropyl)methoxy 806 3-OCH₂CH(OH)CF₃ 807 3-CF₃ 808 4-CF₃ 809 3-CH₂CF₂CF₃ 810 3-CH₂CF₃ 811 3-CH(CF₃)₂ 812 3-CF₂CF₂CF₃ 813 3-phenoxy 814 3-phenyl 815 3-(tetrahydro-2-furyl) 816 isoamyl

817 OCF₃ 818 OCF₂CF₂H 819 OCF₂CF₃ 820 CH₂CF₃ 821 CF₃ 822 CF₃CF₂ 823 cyclopentyl 824 isopropoxy 825 SCF₃ 826 sec-butoxy 827 C(CF₃)₂OH 828 (2-furyl) 829 (3-furyl) 830 isobutyl 831 isobutoxy 832 ethoxy 833 OCH₂CF₃ 834 (2-thienyl) 835 cyclopropyl 836 (3-CF₃-phenoxy) 837 cyclopentoxy 838 (cyclopropyl)methoxy 839 OCH₂CH(OH)CF₃ 840 CH₂CF₂CF₃ 841 CH(CF₃)₂ 842 CH(CF₃)₂ 843 CF₂CF₂CF₃ 844 phenoxy 845 phenyl 846 (tetrahydro-2-furyl) 847 isoamyl 848 propoxy 849 tert-butoxy 850 (2-pyridyl)

852 OCF₃ 852 OCF₂CF₂H 853 OCF₂CF₃ 854 CH₂CF₃ 855 CF₃ 856 CF₃CF₂ 857 cyclopentyl 858 isopropoxy 859 SCF₃ 860 sec-butoxy 861 C(CF₃)₂OH 862 (2-furyl) 863 (3-furyl) 864 isobutyl 865 isobutoxy 866 ethoxy 867 OCH₂CF₃ 868 (2-thienyl) 869 cyclopropyl 870 (3-CF₃-phenoxy) 871 cyclopentoxy 872 (cyclopropyl)methoxy 873 OCH₂CH(OH)CF₃ 874 CH₂CF₂CF₃ 875 CH(CF₃)₂ 876 CH(CF₃)₂ 877 CF₂CF₂CF₃ 878 phenoxy 879 phenyl 880 (tetrahydro-2-furyl) 881 isoamyl 882 propoxy 883 tert-butoxy 884 (2-pyridyl)

Example Table 6. 3-[(N-aryl)[[cycloalkyl]methyl]amino]-halo-2-propanols.

[0330] Example Table 6. 3-[(N-aryl)[[cycloalkyl]methyl]amino]-halo-2-propanols. Ex. Ex. No. R_(SUB1) No. R_(SUB2)

 885 3-isopropyl  909 3-CF₃O-benzyloxy  886 2-Cl, 3-Cl  910 3-CF₃O-benzyloxy  887 3-CF₃O  911 3-F, 5-F-benzyloxy  888 4-F  912 cyclohexylmethylebeoxy  889 4-CH₃  913 benzyloxy  890 2-F, 5-Br  914 3-CF₃, 5-CF₃-benzyloxy  891 4-Cl, 3-CH₃CH₂  915 4-CF₃O-benzyloxy  892 3-CH₃CH₂  916 4-CH₃CH₂-benzyloxy  893 3-CH₃, 5-CH₃  917 isopropoxy  894 3-(CH₃)₃C  918 3-CF₃-benzyl  895 4-F, 3-CH₃  919 isopropylthio  896 3-Cl, 4-Cl  920 cyclopentoxy  897 3,4-(CH₂)₄  921 3-Cl-5-pyridinyloxy  898 3-HCF₂CF₂O  922 3-CF₃S-benzyloxy  899 3-CHF₂O  923 3-CH₃, 4-CH₃-benzyloxy  900 3-(CH₃)₂N  924 2-F, 3-CF₃-benzyloxy  901 3-cyclopropyl  925 3-F, 5-CF₃-benzyloxy  902 3-(2-furyl)  926 4-(CH₃)₂CH-benzyloxy  903 3-CF₃CF₂  927 1-phenylethoxy  904 4-NH₂  928 4-F, 3-CH₃-benzoyl  905 3-CH₃, 4-CH₃, 5-CH₃  929 3-CF₃-phenyl  906 4-CH₃CH₂CH₂O  930 4-CH₃O-phenylamino  907 3-CF₃  931 cyclopropoxy  908 2-NO₂  932 4-NO₂-phenylthio

 933 3-isopropyl  957 3-CF₃O-benzyloxy  934 2-Cl, 3-Cl  958 3-CF₃-benzyloxy  935 3-CF₃O  959 3-F, 5-F-benzyloxy  936 4-F  960 cyclohexylmethyleneoxy  937 4-CH₃  961 benzyloxy  938 2-F, 5-Br  962 3-CF₃, 5-CF₃-benzyloxy  939 4-Cl, 3-CH₃CH₂  963 4-CF₃O-benzyloxy  940 3-CH₃CH₂  964 4-CH₃CH₂-benzyloxy  941 3-CH₃, 5-CH₃  965 isopropoxy  942 3-(CH₃)₃C  966 3-CF₃-benzyl  943 4-F, 3-CH₃  967 isopropylthio  944 3-Cl, 4-Cl  968 cyclopentoxy  945 3,4-(CH₂)₄  969 3-Cl-5-pyridinyloxy  946 3-HCF₂CF₂O  970 3-CF₃S-benzyloxy  947 3-CHF₂O  971 3-CH₃, 4-CH₃-benzyloxy  948 3-(CH₃)₂N  972 2-F, 3-CF₃-benzyloxy  949 3-cyclopropyl  973 3-F, 5-CF₃-benzyloxy  950 3-(2-furyl)  974 4-(CH₃)₂CH-benzyloxy  951 3-CF₃CF₂  975 1-phenylethoxy  952 4-NH₂  976 4-F, 3-CH₃-benzoyl  953 3-CH₃, 4-CH₃, 5-CH₃  977 3-CF₃-phenyl  954 4-CH₃CH₂CH₂O  978 4-CH₃O-phenylamino  955 3-CF₃  979 cyclopropoxy  956 2-NO₂  980 4-NO₂-phenylthio

 981 3-isopropyl 1005 3-CF₃O-benzyloxy  982 2-Cl, 3-Cl 1006 3-CF₃-benzyloxy  983 3-CF₃O 1007 3-F, 5-F-benzyloxy  984 4-F 1008 cyclohexylmethyleneoxy  985 4-CH₃ 1009 benzyloxy  986 2-F, 5-Br 1010 3-CF₃, 5-CF₃-benzyloxy  987 4-F, 3-CF₃ 1011 4-CF₃O-benzyloxy  988 3-CH₃CH₂ 1012 4-CH₃CH₂-benzyloxy  989 3-CH₃, 5-CH₃ 1013 isopropoxy  990 3-(CH₃)₃C 1014 3-CF₃-benzyl  991 4-F, 3-CH₃ 1015 isopropylthio  992 3-Cl, 4-Cl 1016 cyclopentoxy  993 3,4-(CH₂)₄ 1017 3-Cl-5-pyridinyloxy  994 3-HCF₂CF₂O 1018 3-CF₃S-benzyoxy  995 3-CHF₂O 1019 3-CH₃, 4-CH₃- benzyloxy  996 3-(CH₃)₂N 1020 2-F, 3-CF₃-benzyloxy  997 3-cyclopropyl 1021 3-F, 5-CF₃-benzyloxy  998 3-(2-furyl) 1022 4-(CH₃)₂CH-benzyloxy  999 3-CF₃CF₂ 1023 1-phenylethoxy 1000 4-NH₂ 1024 4-F, 3-CH₃-benzoyl 1001 3-CH₃, 4-CH₃, 5-CH₃ 1025 3-CF₃-phenyl 1002 4-CH₃CH₂CH₂O 1026 4-CH₃O-phenylamino 1003 3-CF₃ 1027 cyclopropoxy 1004 2-NO₂ 1028 4-NO₂-phenylthio

1029 3-isopropyl 1053 3-CF₃O-benzyloxy 1030 2-Cl, 3-Cl 1054 3-CF₃-benzyloxy 1031 3-CF₃O 1055 3-F, 5-F-benzyloxy 1032 4-F 1056 cyclohexylmethyleneoxy 1033 4-CH₃ 1057 benzyloxy 1034 2-F, 5-Br 1058 3-CF₃, 5-CF₃-benzyloxy 1035 4-Cl, 3-CH₃CH₂ 1059 4-CF₃O-benzyloxy 1036 3-CH₃CH₂ 1060 4-CH₃CH₂-benzyloxy 1037 3-CH₃, 5-CH₃ 1061 isopropoxy 1038 3-(CH₃)₃C 1062 3-CF₃-benzyl 1039 4-F, 3-CH₃ 1063 isopropylthio 1040 3-Cl, 4-Cl 1064 cyclopentoxy 1041 3,4-(CH₂)₄ 1065 3-Cl-5-pyridinyloxy 1042 3-HCF₂CF₂O 1066 3-CF₃S-benzyloxy 1043 3-CHF₂O 1067 3-CH₃, 4-CH₃-benzyloxy 1044 3-(CH₃)₂N 1068 2-F, 3-CF₃-benzyloxy 1045 3-cyclopropyl 1069 3-F, 5-CF₃-benzyloxy 1046 3-(2-furyl) 1070 4-(CH₃)₂CH-benzyloxy 1047 3-CF₃CF₂ 1071 1-phenylethoxy 1048 4-NH₂ 1072 4-F, 3-CH₃-benzoyl 1049 3-CH₃, 4-CH₃, 5-CH₃ 1073 3-CF₃-phenyl 1050 4-CH₃CH₂CH₂O 1074 4-CH₃OO-phenylamino 1051 3-CF₃ 1075 cyclopropoxy 1052 2-NO₂ 1076 4-NO₂-phenylthio

1077 3-isopropyl 1101 3-CF₃O-benzyloxy 1078 2-Cl, 3-Cl 1102 3-CF₃-benzyloxy 1079 3-CF₃O 1103 3-F, 5-F-benzyloxy 1080 4-F 1104 cyclohexylmethyleneoxy 1081 4-CH₃ 1105 benzyloxy 1082 2-F, 5-Br 1106 3-CF₃, 5-CF₃-benzyloxy 1083 4-Cl, 3-CH₃CH₂ 1107 4-CF₃O-benzyloxy 1084 3-CH₃CH₂ 1108 4-CH₃CH₂-benzyloxy 1085 3-CH₃, 5-CH₃ 1109 isopropoxy 1086 3-(CH₃)₃C 1110 3-CF₃-benzyl 1087 4-F, 3-CH₃ 1111 isopropylthio 1088 3-Cl, 4-Cl 1112 cyclopentoxy 1089 3,4-(CH₂)₄ 1113 3-Cl-5-pyridinyloxy 1090 3-HCF₂CF₂O 1114 3-CF₃S-benzyloxy 1091 3-CHF₂O 1115 3-CH₃, 4-CH₃-benzyloxy 1092 3-(CH₃)₂N 1116 2-F, 3-CF₃-benzyloxy 1093 3-cyclopropyl 1117 3-F, 5-CF₃-benzyloxy 1094 3-(2-furyl) 1118 4-(CH₃)₂CH-benzyloxy 1095 3-CF₃CF₂ 1119 1-phenylethoxy 1096 4-NH₂ 1120 4-F, 3-CH₃-benzoyl 1097 3-CH₃, 4-CH₃, 5-CH₃ 1121 3-CF₃-phenyl 1098 4-CH₃CH₂CH₂O 1122 4-CH₃O-phenylamino 1099 3-CF₃ 1123 cyclopropoxy 1100 2-NO₂ 1124 4-NO₂-phenylthio

1125 3-isopropyl 1149 3-CF₃O-benzyloxy 1126 2-Cl, 3-Cl 1150 3-CF₃-benzyloxy 1127 3-CF₃O 1151 3-F, 5-F-benzyloxy 1128 4-F 1152 cyclohexylmethyleneoxy 1129 4-CH₃ 1153 benzyloxy 1130 2-F, 5-Br 1154 3-CF₃, 5-CF₃-benzyloxy 1131 4-Cl, 3-CH₃CH₂ 1155 4-CF₃O-benzyloxy 1132 3-CH₃CH₂ 1156 4-CH₃CH₂-benzyloxy 1133 3-CH₃, 5-CH₃ 1157 isopropoxy 1134 3-(CH₃)₃C 1158 3-CF₃-benzyl 1135 4-F, 3-CH₃ 1159 isopropylthio 1136 3-Cl, 4-Cl 1160 cyclopentoxy 1137 3,4-(CH₂)₄ 1161 3-Cl-5-pyridinyloxy 1138 3-HCF₂CF₂O 1162 3-CF₃S-benzyloxy 1139 3-CHF₂O 1163 3-CH₃, 4-CH₃-benzyloxy 1140 3-(CH₃)₂N 1164 2-F, 3-CF₂-benzyloxy 1141 3-cyclopropyl 1165 3-F, 5-CF₃-benzyloxy 1142 3-(2-furyl) 1166 4-(CH₃)₂CH-benzyloxy 1143 3-CF₃CF₂ 1167 1-phenylethoxy 1144 4-NH₂ 1168 4-F, 3-CH₃-benzoyl 1145 3-CH₃, 4-CH₃, 5-CH₃ 1169 3-CF₃-phenyl 1146 4-CH₃CH₂CH₂O 1170 4-CH₃O-phenylamino 1147 3-CF₃ 1171 cyclopropoxy 1148 2-NO₂ 1172 4-NO₂-phenylthio

1173 3-isopropyl 1197 3-CF₃O-benzyloxy 1174 2-Cl, 3-Cl 1198 3-CF₃-benzyloxy 1175 3-CF₃O 1199 3-F, 5-F-benzyloxy 1176 4-F 1200 cyclohexylmethyleneoxy 1177 4-CH₃ 1201 benzyloxy 1178 2-F, 5-Br 1202 3-CF₃, 5-CF₃-benzyloxy 1179 4-Cl, 3-CH₃CH₂ 1203 4-CF₃O-benzyloxy 1180 3-CH₃CH₂ 1204 4-CH₃CH₂-benzyloxy 1181 3-CH₃, 5-CH₃ 1205 isopropoxy 1182 3-(CH₃)₃C 1206 3-CF₃-benzyl 1183 4-F, 3-CH₃ 1207 isopropylthio 1184 3-Cl, 4-Cl 1208 cyclopentoxy 1185 3,4-(CH₂)₄ 1209 3-Cl-5-pyridinyloxy 1186 3-HCF₂CF₂O 1210 3-CF₃S-benzyloxy 1187 3-CHF₂O 1211 3-CH₃, 4-CH₃-benzyloxy 1188 3-(CH₃)₂N 1212 2-F, 3-CF₃-benzyloxy 1189 3-cyclopropyl 1213 3-F, 5-CF₃-benzyloxy 1190 3-(2-furyl) 1214 4-(CH₃)₂CH-benzyloxy 1191 3-CF₃CF₂ 1215 1-phenylethoxy 1192 4-NH₂ 1216 4-F, 3-CH₃-benzoyl 1193 3-CH₃, 4-CH₂, 5-CH₃ 1217 3-CF₃-phenyl 1194 4-CH₃CH₂CH₂O 1218 4-CH₃O-phenylamino 1195 3-CF₃ 1219 cyclopropxy 1196 2-NO₂ 1220 4-NO₂-phenylthio

1221 3-isopropyl 1245 3-CF₃O-benzyloxy 1222 2-Cl, 3-Cl 1246 3-CF₃-benzyloxy 1223 3-CF₃O 1247 3-F, 5-F-benzyloxy 1224 4-F 1248 cyclohexylmethyleneoxy 1225 4-CH₃ 1249 benzyloxy 1226 2-F, 5-Br 1250 3-CF₃, 5-CF₃-benzyloxy 1227 4-Cl, 3-CH₃CH₂ 1251 4-CF₃O-benzyloxy 1228 3-CH₃CH₂ 1252 4-CH₃CH₂-benzyloxy 1229 3-CH₃, 5-CH₃ 1253 isopropoxy 1230 3-(CH₃)₃C 1254 3-CF₃-benzyl 1231 4-F, 3-CH₃ 1255 isopropylthio 1232 3-Cl, 4-Cl 1256 cyclopentoxy 1233 3,4-(CH₂)₄ 1257 3-Cl-5-pyridinyloxy 1234 3-HCF₂CF₂O 1258 3-CF₃S-benzyloxy 1235 3-CHF₂O 1259 3-CH₃, 4-CH₃-benzyloxy 1236 3-(CH₃)₂N 1260 2-F, 3-CF₃-benzyloxy 1237 3-cyclopropyl 1261 3-F, 5-CF₃-benzyloxy 1238 3-(2-furyl) 1262 4-(CH₃)₂CH-benzyloxy 1239 3-CF₃CF₂ 1263 1-phenylethoxy 1240 4-NH₂ 1264 4-F, 3-CH₃-benzoyl 1241 3-CH₃, 4-CH₃, 5-CH₃ 1265 3-CF₃-phenyl 1242 4-CH₃CH₂CH₂O 1266 4-CH₃O-phenylamino 1243 3-CF₃ 1267 cyclopropoxy 1244 2-NO₂ 1268 4-NO₂-phenylthio

1269 3-isopropyl 1293 3-CF₃O-benzyloxy 1270 2-Cl, 3-Cl 1294 3-CF₃-benzyloxy 1271 3-CF₃O 1295 3-F, 5-F-benzyloxy 1272 4-F 1296 cyclohexylmethyleneoxy 1273 4-CH₃ 1297 benzyloxy 1274 2-F, 5-Br 1298 3-CF₃, 5-CF₃-benzyloxy 1275 4-Cl, 3-CH₃CH₂ 1299 4-CF₃O-benzyloxy 1276 3-CH₃CH₂ 1300 4-CH₃CH₂-benzyloxy 1277 3-CH₃, 5-CH₃ 1301 isopropoxy 1278 3-(CH₃)₃C 1302 3-CF₃-benzyl 1279 4-F, 3-CH₃ 1303 isopropylthio 1280 3-Cl, 4-Cl 1304 cyclopentoxy 1281 3,4-(CH₂)₄ 1305 3-Cl-5-pyridinyloxy 1282 3-HCF₂CF₂O 1306 3-CF₃S-benzyloxy 1283 3-CHF₂O 1307 3-CH₃, 4-CH₃-benzyloxy 1284 3-(CH₃)₂N 1308 2-F, 3-CF₃-benzyloxy 1285 3-cyclopropyl 1309 3-F, 5-CF₃-benzyloxy 1286 3-(2-furyl) 1310 4-(CH₃)₂CH-benzyloxy 1287 3-CF₃CF₂ 1311 1-phenylethoxy 1288 4-NH₂ 1312 4-F, 3-CH₃-benzoyl 1289 3-CH₃, 4-CH₃, 5-CH₃ 1313 3-CF₃-phenyl 1290 4-CH₃CH₂CH₂O 1314 4-CH₃O-phenylamino 1291 3-CF₃ 1315 cyclopropoxy 1292 2-NO₂ 1316 4-NO₂-phenylthio

1317 3-isopropyl 1341 3-CF₃O-benzyloxy 1318 2-Cl, 3-Cl 1342 3-CF₃-benzyloxy 1319 3-CF₃O 1343 3-F, 5-F-benzyloxy 1320 4-F 1344 cyclohexylmethyleneoxy 1321 4-CH₃ 1345 benzyloxy 1322 2-F, 5-Br 1346 3-CF₃, 5-CF₃-benzyloxy 1323 4-Cl, 3-CH₃CH₂ 1347 3-CF₃, 5-CF₃-benzyloxy 1324 3-CH₃CH₂ 1348 4-CH₃CH₂-benzyloxy 1325 3-CH₃, 5-CH₃ 1349 siopropoxy 1326 3-(CH₃)₃C 1350 3-CF₃-benzyl 1327 4-F, 3-CH₃ 1351 isopropylthio 1328 3-Cl, 4-Cl 1352 cyclopentoxy 1329 3,4-(CH₂)₄ 1353 3-Cl-5-pyridinyloxy 1330 3-HCF₂CF₂O 1354 3-CF₃S-benzyloxy 1331 3-CHF₂O 1355 3-CH₃, 4-CH₃-benzyloxy 1332 3-(CH₃)₂N 1356 2-F, 3-CF₃-benzyloxy 1333 3-cyclopropyl 1357 3-F, 5-CF₃-benzyloxy 1334 3-(2-furyl) 1358 4-(CH₃)₂CH-benzyloxy 1335 3-CF₃CF₂ 1359 1-phenylethoxy 1336 4-NH₂ 1360 4-F, 3-CH₃-benzoyl 1337 3-CH₃, 4-CH₃, 5-CH₃ 1361 3-CF₃-phenyl 1338 4-CH₃CH₂CH₂O 1362 4-CH₃O-phenylamino 1339 3-CF₃ 1363 cyclopropoxy 1340 2-NO₂ 1364 4-NO₂-phenylthio

1365 3-isopropyl 1389 3-CF₃O-benzyloxy 1366 2-Cl, 3-Cl 1390 3-CF₃-benzyloxy 1367 3-CF₃O 1391 3-F, 5-F-benzyloxy 1368 4-F 1392 cyclohexylmethyleneoxy 1369 4-CH₃ 1393 benzyloxy 1370 2-F, 5-Br 1394 3-CF₃, 5-CF₃-benzyloxy 1371 4-Cl, 3-CH₃CH₂ 1395 4-CF₃O-benzyloxy 1372 3-CH₃CH₂ 1396 4-CH₃CH₂-benzyloxy 1373 3-CH₃, 5-CH₃ 1397 isopropoxy 1374 3-(CH₃)₃C 1398 3-CF₃-benzyl 1375 4-F, 3-CH₃ 1399 isopropylthio 1376 3-Cl, 4-Cl 1400 cyclopentoxy 1377 3,4-(CH₂)₄ 1401 3-Cl-5-pyridinyloxy 1378 3-HCF₂CF₂O 1402 3-CF₃S-benzyloxy 1379 3-CHF₂O 1403 3-CH₃, 4-CH₃-benzyloxy 1380 3-(CH₃)₂N 1404 2-F, 3-CF₃-benzyloxy 1381 3-cyclopropyl 1405 3-F, 5-CF₃-benzyloxy 1382 3-(2-furyl) 1406 4-(CH₃)₂CH-benzyloxy 1383 3-CF₃CF₂ 1407 1-phenylethoxy 1384 4-NH₂ 1408 4-F, 3-CH₃-benzoyl 1385 3-CH₃, 4-CH₃, 5-CH₃ 1409 3-CF₃-phenyl 1386 4-CH₃CH₂CH₂O 1410 4-CH₃O-phenylamino 1387 3-CF₃ 1411 cyclopropoxy 1388 2-NO₂ 1412 4-NO₂-phenylthio

1413 3-isopropyl 1437 3-CF₃O-benzyloxy 1414 2-Cl, 3-Cl 1438 3-CF₃-benzyloxy 1415 3-CF₃O 1439 3-F, 5-F-benzyloxy 1416 4-F 1440 cyclohexylmethyleneoxy 1417 4-CH₃ 1441 benzyloxy 1418 2-F, 5-Br 1442 3-CF₃, 5-CF₃-benzyloxy 1419 4-Cl, 3-CH₃CH₂ 1443 4-CF₃O-benzyloxy 1420 3-CH₃CH₂ 1444 4-CH₃CH₂-benzyloxy 1421 3-CH₃, 5-CH₃ 1445 isopropoxy 1422 3-(CH₃)₃C 1446 3-CF₃-benzyl 1423 4-F, 3-CH₃ 1447 isopropylthio 1424 3-Cl, 4-Cl 1448 cyclopentoxy 1425 3,4-(CH₂)₄ 1449 3-Cl-5-pyridinyloxy 1426 3-HCF₂CF₂O 1450 3-CF₃S-benzyloxy 1427 3-CHF₂O 1451 3-CH₃, 4-CH₃-benzyloxy 1428 3-(CH₃)₂N 1452 2-F, 3-CF₃-benzyloxy 1429 3-cyclopropyl 1453 3-F, 5-CF₃-benzyloxy 1430 3-(2-furyl) 1454 4-(CH₃)₂CH-benzyloxy 1431 3-CF₃CF₂ 1455 1-phenylethoxy 1432 4-NH₂ 1456 4-F, 3-CH₃-benzoyl 1433 3-CH₃, 4-CH₃, 5-CH₃ 1457 3-CF₃-phenyl 1434 4-CH₃CH₂CH₂O 1458 4-CH₃O-phenylamino 1435 3-CF₃ 1459 cyclopropoxy 1436 2-NO₂ 1460 4-NO₂phenylthio

Example Table 7. 3-[(N-aryl)[[haloalkyl]methyl]amino]-halo-2-propanols.

[0331] Example Table 7. 3-[(N-aryl)[[haloalkyl]methyl]amino]-halo-2-propanols. Ex. Ex. No. R_(SUB1) No. R_(SUB2)

1461 3-isopropyl 1485 3-CF₃O-benzyloxy 1462 2-Cl, 3-Cl 1486 3-CF₃-benzyloxy 1463 3-CF₃O 1487 3-F, 5-F-benzyloxy 1464 4-F 1488 cyclohexylmethyleneoxy 1465 4-CH₃ 1489 benzyloxy 1466 2-F, 5-Br 1490 3-CF₃, 5-CF₃-benzyloxy 1467 4-Cl, 3-CH₃CH₂ 1491 4-CF₃O-benzyloxy 1468 3-CH₃CH₂ 1492 4-CH₃CH₂-benzyloxy 1469 3-CH₃, 5-CH₃ 1493 isopropoxy 1470 3-(CH₃)₃C 1494 3-CF₃-benzyl 1471 4-F, 3-CH₃ 1495 isopropylthio 1472 3-Cl, 4-Cl 1496 cyclopentoxy 1473 3,4-(CH₂)₄ 1497 3-Cl-5-pyridinyloxy 1474 3-HCF₂CF₂O 1498 3-CF₃S-benzyloxy 1475 3-CHF₂O 1499 3-CH₃, 4-CH₃-benzyloxy 1476 3-(CH₃)₂N 1500 2-F, 3-CF₃-benzyloxy 1477 3-cyclopropyl 1501 3-F, 5-CF₃-benzyloxy 1478 3-(2-furyl) 1502 4-(CH₃)₂CH-benzyloxy 1479 3-CF₃CF₂ 1503 1-phenylethoxy 1480 4-NH₂ 1504 4-F, 3-CH₃-benzoyl 1481 3-CH₃, 4-CH₃, 5-CH₃ 1505 3-CF₃-phenyl 1482 4-CH₃CH₂CH₂O 1506 4-CH₃O-phenylamino 1483 3-CF₃ 1507 cyclopropoxy 1484 2-NO₂ 1508 4-NO₂-phenylthio

1509 3-isopropyl 1533 3-CF₃O-benzyloxy 1510 2-Cl, 3-Cl 1534 3-CF₃-benzyloxy 1511 3-CF₃O 1535 3-F, 5-F-benzyloxy 1512 4-F 1536 cyclohexylmethyleneoxy 1513 4-CH₃ 1537 benzyloxy 1514 2-F, 5-Br 1538 3-CF₃, 5-CF₃-benzyloxy 1515 4-Cl, 3-CH₃CH₂ 1539 4-CF₃O-benzyloxy 1516 3-CH₃CH₂ 1540 4-CH₃CH₂-benzyloxy 1517 3-CH₃, 5-CH₃ 1541 isopropoxy 1518 3-(CH₃)₃C 1542 3-CF₃-benzyl 1519 4-F, 3-CH₃ 1543 isopropylthio 1520 3-Cl, 4-Cl 1544 cyclopentoxy 1521 3,4-(CH₂)₄ 1545 3-Cl-5-pyridinyloxy 1522 3-HCF₂CF₂O 1546 3-CF₃S-benzyloxy 1523 3-CHF₂O 1547 3-CH₃, 4-CH₃-benzyloxy 1524 3-(CH₃)₂N 1548 2-F, 3-CF₃-benzyloxy 1525 3-cyclopropyl 1549 3-F, 5-CF₃-benzyloxy 1526 3-(2-furyl) 1550 4-(CH₃)₂CH-benzyloxy 1527 3-CF₃CF₂ 1551 1-phenylethoxy 1528 4-NH₂ 1552 4-F, 3-CH₃-benzoyl 1529 3-CH₃, 4-CH₃, 5-CH₃ 1553 3-CF₃-phenyl 1530 4-CH₃CH₂CH₂O 1554 4-CH₃O-phenylamino 1531 3-CF₂ 1555 cyclopropoxy 1532 2-NO₂ 1556 4-NO₂-phenylthio

1557 3-isopropyl 1581 3-CF₃O-benzyloxy 1558 2-Cl, 3-Cl 1582 3-CF₃-benzyloxy 1559 3-CF₃O 1583 3-F, 5-F-benzyloxy 1560 4-F 1584 cyclohexylmethyleneoxy 1561 4-CH₃ 1585 benzyloxy 1562 2-F, 5-Br 1586 3-CF₃, 5-CF₃-benzyloxy 1563 4-Cl, 3-CH₃CH₂ 1587 4-CF₃O-benzyloxy 1564 3-CH₃CH₂ 1588 4-CH₃CH₂-benzyloxy 1565 3-CH₃, 5-CH₃ 1589 isopropoxy 1566 3-(CH₃)₃C 1590 3-CF₃-benzyl 1567 4-F, 3-CH₃ 1591 isopropylthio 1568 3-Cl, 4-Cl 1592 cyclopentoxy 1569 3,4-(CH₂)₄ 1593 3-Cl-5-pyridinyloxy 1570 3-HCF₂CF₂O 1594 3-CF₃S-benzyloxy 1571 3-CHF₂O 1595 3-CH₃, 4-CH₃-benzyloxy 1572 3-(CH₃)₂N 1596 2-F, 3-CF₃-benzyloxy 1573 3-cyclopropyl 1597 3-F, 5-CF₃-benzyloxy 1574 3-(2-furyl) 1598 4-(CH₃)₂CH-benzyloxy 1575 3-CF₃CF₂ 1599 1-phenylethoxy 1576 4-NH₂ 1600 4-F, 3-CH₃-benzoyl 1577 3-CH₃, 4-CH₃, 5-CH₃ 1601 3-CF₃-phenyl 1578 4-CH₃CH₂CH₂O 1602 4-CH₃O-phenylamino 1579 3-CF₃ 1603 cyclopropoxy 1580 2-NO₂ 1604 4-NO₂-phenylthio

1605 3-isopropyl 1629 3-CF₃O-benzyloxy 1606 2-Cl, 3-Cl 1630 3-CF₃-benzyloxy 1607 3-CF₃O 1631 3-F, 5-F-benzyloxy 1608 4-F 1632 cyclohexylmethyleneoxy 1609 4-CH₃ 1633 benzyloxy 1610 2-F, 5-Br 1634 3-CF₃, 5-CF₃-benzyloxy 1611 4-Cl, 3-CH₃CH₂ 1635 4-CF₃O-benzyloxy 1612 3-CH₃CH₂ 1636 4-CH₃CH₂-benzyloxy 1613 3-CH₃, 5-CH₃ 1637 isopropoxy 1614 3-(CH₃)₃C 1638 3-CF₃-benzyl 1615 4-F, 3-CH₃ 1639 isopropylthio 1616 3-Cl, 4-Cl 1640 cyclopentoxy 1617 3,4-(CH₂)₄ 1641 3-Cl-5-pyridinyloxy 1618 3-HCF₂CF₂O 1642 3-CF₃S-benzyloxy 1619 3-CHF₂O 1643 3-CH₃, 4-CH₃-benzyloxy 1620 3-(CH₃)₂N 1644 2-F, 3-CF₃-benzyloxy 1621 3-cyclopropyl 1645 3-F, 5-CF₃benzyloxy 1622 3-(2-furyl) 1646 4-(CH₃)₂CH-benzyloxy 1623 3-CF₃CF₂ 1647 1-phenylethoxy 1624 4-NH₂ 1648 4-F, 3-CH₃-benzoyl 1625 3-CH₃, 4-CH₃, 5-CH₃ 1649 3-CF₃-phenyl 1626 4-CH₃CH₂CH₂O 1650 4-CH₃O-phenylamino 1627 3-CF₃ 1651 cyclopropyl 1628 2-NO₂ 1652 4-NO₂-phenylthio

BIOASSAYS

[0332] CETP Activity In Vitro

[0333] ASSAY OF CETP INHIBITION USING PURIFIED COMPONENTS (RECONSTITUTED BUFFER ASSAY)

[0334] The ability of compounds to inhibit CETP activity was assessed using an in vitro assay that measured the rate of transfer of radiolabeled cholesteryl ester ([³H]CE) from HDL donor particles to LDL acceptor particles. Details of the assay are provided by Glenn, K. C. et al. (Glenn and Melton, “Quantification of Cholesteryl Ester Transfer Protein (CETP): A) CETP Activity and B) Immunochemical Assay of CETP Protein,” Meth. Enzymol., 263, 339-351 (1996)). Human recombinant CETP can be obtained from the serum-free conditioned medium of CHO cells transfected with a cDNA for CETP and purified as described by Wang, S. et al. (J. Biol. Chem. 267, 17487-17490 (1992)). To measure CETP activity, [³H]CE-labeled-HDL, LDL, CETP and assay buffer (50 mM tris(hydroxymethyl)aminomethane, pH 7.4; 150 mM sodium chloride; 2 mM ethylenediamine-tetraacetic acid (EDTA); 1% bovine serum albumin) were incubated in a final volume of 200 μL, for 2 hours at 37° C. in 96 well plates. Inhibitors were included in the assay by diluting from a 10 mM DMSO stock solution into 16% (v/v) aqueous DMSO so that the final concentration of inhibitor was 800 μM. The inhibitors were then diluted 1:1 with CETP in assay buffer, and then 25 μL of that solution was mixed with 175 μL of lipoprotein pool for assay. Following incubation, LDL was differentially precipitated by the addition of 50 μL of 1% (w/v) dextran sulfate/0.5M magnesium chloride, mixed by vortex, and incubated at room temperature for 10 minutes. A potion of the solution (200 μL) was transferred to a filter plate (Millipore). After filtration, the radioactivity present in the precipitated LDL was measured by liquid scintillation counting. Correction for non-specific transfer or precipitation was made by including samples that do not contain CETP. The rate of [³H]CE transfer using this assay was linear with respect to time and CETP concentration, up to 25-30% of [³H]CE transferred.

[0335] The potency of test compounds was determined by performing the above described assay in the presence of varying concentrations of the test compounds and determining the concentration required for 50% inhibition of transfer of [³H]CE from HDL to LDL. This value was defined as the IC₅₀. The IC₅₀ values determined from this assay are accurate when the IC₅₀ is greater than 10 nM. In the case where compounds have greater inhibitory potency, accurate measurements of IC₅₀ may be determined using longer incubation times (up to 18 hours) and lower final concentrations of CETP (<50 nM).

[0336] Examples of IC₅₀ values determined by these methods are summarized in Table 3.

Table 3. Inhibition of CETP Activity by Examples in Reconstituted Buffer Assay.

[0337] Ex. IC₅₀ No. (μM) 18 11  1 15 16 15  9 18  4 20 11 45  8 45 10 50 14 55 12 60 17 60 13 80  7 100   2 100   6 >100.0  5 >100.0 15 >100.0  3 not tested 

What we claim is:
 1. A compound having the formula:

or a pharmaceutically-acceptable salt thereof, wherein; n is an integer selected from 1 through 4; A and Q are independently selected from the group consisting of —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H,

with the provisos that one of A and Q must be AQ-1 and that one of A and Q must be selected from the group consisting of AQ-2 and —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H; T is selected from the group consisting of a single covalent bond, O, S, S(O), S(O)₂, C(R₃₃)═C(R₃₅), and C≡C; v is an integer selected from 0 through 1 with the proviso that v is 1 when any one of R₃₃, R₃₄, R₃₅, and R₃₆ is aryl or heteroaryl; u and w are integers independently selected from 0 through 6; A₁ is C(R₃₀); D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ is a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ is O, no more than one of D₁, D₂, J₁, J₂ and K, is S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ are N; B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C, C(R₃₀), N, O, S and a covalent bond with the provisos that no more than 5 of B₁, B₂, D₃, D₄, 13, 14 and K₂ are a covalent bond, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are O, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are S, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are simultaneously O and S, and no more than two of B₁, B₂, D_(3,) D₄, J₃, J₄ and K₂ are N; B₁ and D₃, D₃ and J₃, J₃ and K₂, K₂ and J₄, J₄ and D₄, and D₄ and B₂ are independently selected to form an in-ring spacer pair wherein said spacer pair is selected from the group consisting of C(R₃₃)═C(R₃₅) and N═N with the provisos that AQ-2 must be a ring of at least five contiguous members, that no more than two of the group of said spacer pairs are simultaneously C(R₃₃)═C(R₃₅), and that no more than one of the group of said spacer pairs can N═N unless the other spacer pairs is other than C(R₃₃)═C(R₃₅), O, N, and S: R₁₆ is selected from the group consisting of hydrido, alkyl, acyl, aroyl, heteroaroyl, and trialkylsilyl; X is selected from the group consisting of O, H, F, S, S(O). NH, N(OH), N(alkyl), and N(alkoxy) with the proviso that there is no R₁₆ wherein X is H or F; R₁ is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl, and haloalkenyloxyalkyl; R₂ is selected from the group consisting of hydrido, aryl, aralkyl, alkyl, alkenyl, alkenyloxyalkyl, haloalkyl, haloalkenyl, halocycloalkyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, dicyanoalkyl, and carboalkoxycyanoalkyl; R₃ is selected from the group consisting of hydrido, hydroxy, cyano, aryl, aralkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, heteroaryl, alkenyloxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl; Y is selected from a group consisting of a covalent single bond, (C(R₁₄)₂)_(q) wherein q is an integer selected from 1 through 4 and (CH(R₁₄))_(g)—O—(CH(R₁₄))_(p) wherein g and p are integers independently selected from 0 through 2; R₁₄ is selected from the group consisting of hydrido, hydroxy, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, carboxamidoalkyl; Z is selected from the group consisting of covalent single bond, (C(R₁₅)₂)_(q) wherein q is an integer selected from 1 through 2, and (CH(R₁₅))_(j)—O—(CH(R₁₅)) wherein j and k are integers independently selected from 0 through 2; R₁₅ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl; R₃₀ is selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl with the proviso that R₃₀ is selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; R₃₀, when bonded to A₁, is taken together to form an intra-ring linear spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the point of bonding of a group selected from the group consisting of R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ wherein said intra-ring linear spacer is selected from the group consisting of a covalent single bond and a spacer moiety having from 1 through 6 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 10 contiguous members, a cycloalkenyl having from 5 through 10 contiguous members, and a heterocyclyl having from 5 through 10 contiguous members; R₃₀, when bonded to A₁, is taken together to form an intra-ring branched spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the points of bonding of each member of any one of substituent pairs selected from the group consisting of subsitituent pairs R₁₀ and R₁₁, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₀ and R₁₂, R₁₁ and R₃₁, R₁₁ and R₃₂, R ₁₁ and R₁₂, R₃₁ and R₃₂, R₃₁ and R₁₂, and R₃₂ and R₁₂ and wherein said intra-ring branched spacer is selected to form two rings selected from the group consisting of cycloalkyl having from 3 through 10 contiguous members, cycloalkenyl having from 5 through 10 contiguous members, and heterocyclyl having from 5 through 10 contiguous members; R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloal kenyloxy, halocycioalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonaniido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the provisos that R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen, that no more than three of the R₃₃ and R₃₄ substituents are simultaneously selected from other than the group consisting of of hydrido and halo, and that no more than three of the R₃₅ and R₃₆ substituents are simultaneously selected from other than the group consisting of of hydrido and halo: R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are independently selected to be oxo with the provisos that B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C and S, no more than two of R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are simultaneously oxo, and that R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, are used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ are used at the same time; R₉ and R₁₁, R₉ and R₁₂, R₉ and R₁₃, R₉ and R₃₁, R₉ and R₃₂, R₁₀ and R₁₂, R₁₀ and R₁₃, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₁ and R₁₂, R₁₁ and R₁₃, R₁₁ and R₃₂, R₁₂ and R₃₁, R₁₃ and R₃₁, and R₁₃ and R₃₂ are independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from 1 through 3 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, a saturated heterocyclyl having from 5 through 8 contiguous members and a partially saturated heterocyclyl having from 5 through 8 contiguous members with the provisos that no more than one of said group of spacer pairs is used at the same time; R₃₇ and R₃₈ are independently selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, hydroxy, amino, thio, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, cyano, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.
 2. The compound as recited in claim 1 having the formula of:

or a pharmaceutically acceptable salt thereof, wherein; n is an integer selected from 1 through 2; A and Q are independently selected from the group consisting of —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H,

with the provisos that one of A and Q must be AQ-1 and that one of A and Q must be selected from the group consisting of AQ-2 and —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H; T is selected from the group consisting of a single covalent bond, O, S, S(O), S(O)₂, C(R₃₃)═C(R₃₅), and C≡C; v is an integer selected from 0 through 1 with the proviso that v is 1 when any one of R₃₃, R₃₄, R₃₅, and R₃₆ is aryl or heteroaryl; u and w are integers independently selected from 0 through 6; A₁ is C(R₃₀); D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ is a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ is O, no more than one of D₁, D₂, J₁, J₂ and K₁ is S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ are N; B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C, C(R₃₀), N, O, S and a covalent bond with the provisos that no more than 5 of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are a covalent bond, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are O, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are S, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are simultaneously O and S, and no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are N; B₁ and D₃, D₃ and J₃, J₃ and K₂, K₂ and J₄, J₄ and D₄, and D₄ and B₂ are independently selected to form an in-ring spacer pair wherein said spacer pair is selected from the group consisting of C(R₃₃)═C(R₃₅) and N═N with the provisos that AQ-2 must be a ring of at least five contiguous members, that no more than two of the group of said spacer pairs are simultaneously C(R₃₃)═C(R₃₅), and that no more than one of the group of said spacer pairs is N═N unless the other spacer pairs are other than C(R₃₃)═C(R₃₅), O, N, and S; R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl; R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl; R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl; Y is selected from the group consisting of a covalent single bond, (CH₂)_(q) wherein q is an integer selected from 1 through 2, and (CH₂)_(j)—O—(CH₂)_(k) wherein j and k are integers independently selected from 0 through 1; Z is selected from the group consisting of covalent single bond, (CH₂)_(q) wherein q is an integer selected from 1 through 2, and (CH₂)_(j)—O—(CH₂)_(k) wherein j and k are integers independently selected from 0 through 1: R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido, halo, haloalkyl, and alkyl; R₃₀ is selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl with the proviso that R₃₀ is selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; R₃₀, when bonded to A₁, is taken together to form an intra-ring linear spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the point of bonding of a group selected from the group consisting of R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ wherein said intra-ring linear spacer is selected from the group consisting of a covalent single bond and a spacer moiety having from 1 through 6 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 10 contiguous members, a cycloalkenyl having from 5 through 10 contiguous members, and a heterocyclyl having from 5 through 10 contiguous members; R₃₀, when bonded to A₁, is taken together to form an intra-ring branched spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the points of bonding of each member of any one of substituent pairs selected from the group consisting of subsitituent pairs R₁₀ and R₁₁, R₁₀ and R₃₁. R₁₀ and R₃₂, R₁₀ and R₁₂, R₁₁ and R₃₁, R₁₁ and R₃₂, R₁₁ and R₁₂, R₃₁ and R₃₂, R₃₁ and R₁₂, and R₃₂ and R₁₂ and wherein said intra-ring branched spacer is selected to form two rings selected from the group consisting of cycloalkyl having from 3 through 10 contiguous members, cycloalkenyl having from 5 through 10 contiguous members, and heterocyclyl having from 5 through 10 contiguous members: R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the provisos that R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen, that no more than three of the R₃₃ and R₃₄ substituents are simultaneously selected from other than the group consisting of of hydrido and halo, and that no more than three of the R₃₅ and R₃₆ substituents are simultaneously selected from other than the group consistubg of hydrido and halo; R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are independently selected to be oxo with the provisos that B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C and S, no more than two of R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are simultaneously oxo, and that R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ is used at the same time; R₉ and R₁₁, R₉ and R₁₂, R₉ and R₁₃, R₉ and R₃₁, R₉ and R₃₂, R₁₀ and R₁₂, R₁₀ and R₁₃, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₁ and R₁₂, R₁₁ and R₁₃, R₁₁ and R₃₂, R₁₂ and R₃₁, R₁₃ and R₃₁, and R₁₃ and R₃₂ are independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from 1 through 3 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, a saturated heterocyclyl having from 5 through 8 contiguous members and a partially saturated heterocyclyl having from 5 through 8 contiguous members with the provisos that no more than one of said group of spacer pairs is used at the same time; R₃₇ and R₃₈ are independently selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, hydroxy, amino, thio, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, cyano, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.
 3. The compound as recited in claim 2 having the formula of:

or a pharmaceutically acceptable salt thereof, wherein; n is an integer selected from 1 through 2; A and Q are independently selected from the group consisting of —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H,

with the provisos that one of A and Q must be AQ-1P and that one of A and Q must be selected from the group consisting of AQ-2 and —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H; T is selected from the group consisting of a single covalent bond, O, S, S(O), S(O)₂, C(R₃₃)═C(R₃₅), and C≡C; v is an integer selected from 0 through 1 with the proviso that v is 1 when any one of R₃₃, R₃₄, R₃₅, and R₃₆ is aryl or heteroaryl: u and w are integers independently selected from 0 through 6; A₁ is C(R₃₀); B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C, C(R₃₀), N, O, S and a covalent bond with the provisos that no more than 5 of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are a covalent bond, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are O, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are S, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are simultaneously O and S, and no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are N; B₁ and D₃, D₃ and J₃, J₃ and K₂, K₂ and J₄, J₄ and D₄, and D₄ and B₂ are independently selected to form an in-ring spacer pair wherein said spacer pair is selected from the group consisting of C(R₃₃)═C(R₃₅) and N═N with the provisos that AQ-2 must be a ring of at least five contiguous members, that no more than two of the group of said spacer pairs are simultaneously C(R₃₃)═C(R₃₅), and that no more than one of the group of said spacer pairs is N═N unless the other spacer pairs are other than C(R₃₃)═C(R₃₅), O, N, and S; R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl; R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl; R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl; Y is selected from the group consisting of a covalent single bond, (CH₂)_(q) wherein q is an integer selected from 1 through 2, and (CH₂)_(j)—O—(CH₂)_(k) wherein j and k are integers independently selected from 0 through 1; Z is selected from the group consisting of covalent single bond, (CH₂)_(q) wherein q is an integer selected from 1 through 2, and (CH₂)_(j)—O—(CH₂)_(k) wherein j and k are integers independently selected from 0 through 1; R₃₀ is selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl with the proviso that R₃₀ is selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; R₃₀, when bonded to A₁, is taken together to form an intra-ring linear spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the point of bonding of a group selected from the group consisting of R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ wherein said intra-ring linear spacer is selected from the group consisting of a covalent single bond and a spacer moiety having from 1 through 6 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 10 contiguous members, a cycloalkenyl having from 5 through 10 contiguous members, and a heterocyclyl having from 5 through 10 contiguous members; R₃₀, when bonded to A₁, is taken together to form an intra-ring branched spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the points of bonding of each member of any one of substituent pairs selected from the group consisting of subsitituent pairs R₁₀ and R₁₁, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₀ and R₁₂, R₁₁ and R₃₁, R₁₁ and R₃₂, R₁₁ and R₁₂, R₃₁ and R₃₂, R₃₁ and R₁₂, and R₃₂ and R₁₂ and wherein said intra-ring branched spacer is selected to form two rings selected from the group consisting of cycloalkyl having from 3 through 10 contiguous members, cycloalkenyl having from 5 through 10 contiguous members, and heterocyclyl having from 5 through 10 contiguous members; R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂,R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl nionoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the provisos that R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen, that no more than three of the R₃₃ and R₃₄ substituents are simultaneously selected from other than the group consisting of of hydrido and halo, and that no more than three of the R₃₅ and R₃₆ substituents are simultaneously selected from other than the group consistubg of hydrido and halo; R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are independently selected to be oxo with the provisos that B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C and S, no more than two of R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are simultaneously oxo, and that R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ is used at the same time; R₉ and R₁₁, R₉ and R₁₂, R₉ and R₁₃, R₉ and R₃₁, R₉ and R₃₂, R₁₀ and R₁₂, R₁₀ and R₁₃, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₁and R₁₂, R₁₁ and R₁₃, R₁₁ and R₃₂, R₁₂ and R₃₁, R₁₃ and R₃₁, and R₁₃ and R₃₂ are independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from I through 3 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, a saturated heterocyclyl having from 5 through 8 contiguous members and a partially saturated heterocyclyl having from 5 through 8 contiguous members with the provisos that no more than one of said group of spacer pairs is used at the same time; R₃₇ and R₃₈ are independently selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, hydroxy, amino, thio, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, cyano, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.
 4. The compound as recited in claim 3 having the formula of:

or a pharmaceutically acceptable salt thereof, wherein; n is an integer selected from 1 through 2; A is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl and C4C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl; R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl; R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl; Y and Z are independently selected from the group consisting of a covalent single bond, oxy and alkylene; R₄ and R₈ are independently selected from the group consisting of hydrido and halo; R₉ and R₁₃ are halo; R₅, R₆, and R₇ are independently selected from the group consisting of hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl; R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time; R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ are independently selected from the group group consisting of alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl; R₃₀ is selected from the group consisting of alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.
 5. The compound as recited in claim 4 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopent-2-enyl, cyclopent-3-enyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbomenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cyclohex-2-enyl, cyclohex-3-enyl, cycloheptyl, cyclohept-2-enyl, cyclohept-3-enyl, cyclooctyl, cyclooct-2-enyl, cyclooct-3-enyl, cyclooct-4-enyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 2H-2-pyranyl, 2H-3-pyranyl, 2H-4-pyranyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-pyranyl, 2H-pyran-2-one-3-yl, 2H-pyran-2-one-4yl, 2H-pyran-2-one-5yl, 4H-pyran-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, vinyl, phenyl, 4-trifluoromethylphenyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl; R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, ethyl, vinyl, trifluoromethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; Y and Z are independently selected from the group consisting of a covalent single bond, oxy, and methylene with the proviso that only one of Y and Z are simultaneously oxy; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₉ and R₁₃ are fluoro; R₅, R₁₀ and R₁₂ are independently selected from the group consisting of 4-aminophenoxy, benzoyl, benzyl, benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-bromo-2-nitrophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-butoxyphenoxy, chloro, 3-chlorobenzyl, 2-chlorophenoxy, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro4-fluorobenzyl, 3-chloro4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, -chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, cyclobutoxy, cyclobutyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropyl, cyclopropylmethoxy, cyclopropoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, fluoro, 4-fluoro-3-methylbenzyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methylbenzoyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro4-trifluoromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, 3-iodobenzyloxy, isobutyl, isobutylamino, isobutoxy, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxycarbonylbutoxy. 3-methoxycarbonylprop-2-enyloxy, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, phenylsulfonyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoromethylthio; R₆, R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, trifluoromethyl, and trifluoromethoxy; R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl; R₃₀ is selected from the group consisting of chloro, ethoxy, ethyl, fluoro, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, isobutyl, isobutoxy, isopropoxy, isopropyl, isopropylthio, methyl pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, propoxy, propyl, sec-butyl, tert-butoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, trifluoromethoxy, and trifluoromethyl.
 6. The compound as recited in claim 5 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cycloheptyl, cyclooctyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl. 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4-H-4-pyranyl, 4H-pyran-4-one-2-yl, 4-H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is selected from the group consisting of hydrido, methyl, ethyl, phenyl, 4-trifluoromethylphenyl, trifluoromethoxymethyl, 1,1,2,2-tetrafluoroethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl; R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl; Y and Z are independently selected from a covalent single bond and methylene; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₉ and R₁₃ are fluoro: R₅, R₁₀ and R₁₂ are independently selected from the group consisting of benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromophenoxy,4-butoxyphenoxy, 3-chlorobenzyloxy, 2-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy. 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, cyclobutoxy, cyclobutyl, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropylmethoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy,2,3-difluorobenzyloxy, 3,5-difluorobenzyloxy, difluoromethoxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy,3-dimethylaminopbenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 1,3-dioxolan-2-yl, 3-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylbenzyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, isobutoxy, isobutyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, 3-isopropylbenzyloxy, 3-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl. 3-methoxybenzyl, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenxyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy. 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, 3-trifluoromethylthiobenzyloxy, and trifluoromethylthio; R₆, R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl; R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl; R₃₀ is selected from the group consisting of chloro, ethyl, methyl, propyl, fluoro, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, isobutyl, isopropyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, sec-butyl, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, trifluoromethoxy, and trifluoromethyl.
 7. The compound as recited in claim 6 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is hydrido, pentafluoroethyl, and trifluoromethyl; R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl Y is methylene; Z is a covalent single bond; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₉ and R₁₃ are fluoro; R₅, R₁₀ and R₁₂ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy), trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy; R₆, R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl; R₇ is selected from the group consisting of hydrido and fluoro.
 8. The compound as recited in claim 6 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1: A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁: R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is hydrido, pentafluoroethyl, and trifluoromethyl; R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl Y is a covalent single bond; Z is methylene; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₉ and R₁₃ are fluoro; R₅, R₁₀ and R₁₂ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy), trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy; R₆, R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl; R₇ is selected from the group consisting of hydrido and fluoro.
 9. The compound as recited in claim 3 having the formula of:

or a pharmaceutically acceptable salt thereof, wherein; n is an integer selected from 1 through 2; A is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, C3-C8 haloalkenyl, C3-C6 alkoxy C1-C2 alkyl, and C3-C8 hydroxyhaloalkyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond; R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl; R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl; R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl; Y and Z are independently selected from the group consisting of a covalent single bond, oxy and alkylene; R₄ and R₈ are independently selected from the group consisting of hydrido and halo; R₅, R₆, R₇, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl; R₅, and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time;
 10. The compound as recited in claim 9 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of ethyl, 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyltpentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl 1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 1-octynyl, 2-octyl, 1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptynyl, 1-methyl-3-heptynyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptenyl, 1-methyl-3-heptynyl, 1-methyl-4-heptynyl, 1-methyl-5-heptynyl, 3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-4-hexenyl, 1-ethyl-2-hexynyl, 1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-propyl-2-pentynyl, 1-propyl-3-pentynyl, 1-butyl-2-butynyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, 3,3,3-trifluoropropyl, 2-methoxyethyl, 2-ethoxyethyl, 2-propoxyethyl, 2-isopropoxyethyl, 2-butoxyethyl, 2-isobutoxyethyl, 2-sec-butoxyethyl, 2-pentoxyethyl, 2-hexoxyethyl, 3-methoxypropyl, 2-methoxyisopropyl, 3-ethoxypropyl, 2-ethoxyisopropyl, 3-propoxypropyl, 2-propoxyisopropyl, 3-isopropoxypropyl, 2-isopropoxyisopropyl, 3-butoxypropyl, 2-butoxyisopropyl, 3-isobutoxypropyl, 2-isobutoxyisopropyl, 3-pentoxypropyl, and 2-pentoxyisopropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond: R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, vinyl, phenyl, 4-trifluoromethylphenyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl; R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, ethyl, vinyl, trifluoromethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; Y and Z are independently selected from the group consisting of a covalent single bond, oxy, and methylene with the proviso that only one of Y and Z are simultaneously oxy; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₅, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of 4-aminophenoxy, benzoyl, benzyl, benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-bromo-2-nitrophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-butoxyphenoxy, chloro, 3-chlorobenzyl, 2-chlorophenoxy, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro-4-fluorobenzyl, 3-chloro-4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, cyclobutoxy, cyclobutyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropyl, cyclopropylmethoxy, cyclopropoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, fluoro, 4-fluoro-3-methylbenzyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methyl benzoyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, 3-iodobenzyloxy, isobutyl, isobutylamino, isobutoxy, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxycarbonylbutoxy, 3-methoxycarbonylprop-2-enyloxy, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, phenylsulfonyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy. 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethyl benzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoromethylthio; R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of cyano and hydroxy; R₆ is selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, trifluoromethyl, and trifluoromethoxy; R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl.
 11. The compound as recited in claim 10 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of ethyl, 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl pentenyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5octenyl. 6-octenyl, 7-octenyl, 2-octyl, 1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-4-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptenyl,3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-4-hexenyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond; R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is selected from the group consisting of hydrido, methyl, ethyl, phenyl, 4-trifluoromethylphenyl, trifluoromethoxymethyl, 1,1,2,2-tetrafluoroethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl; R₃ is selected from the group consisting of hydrido, phenyl 4-trifluoromethylphenyl, methyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl; Y and Z are independently selected from a covalent single bond and methylene; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₅, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromophenoxy, 4-butoxyphenoxy, 3-chlorobenzyloxy, 2-chlorophenoxy, 4-chloro-3 -ethylphenoxy, 4-chloro-3 -methylphenoxy, 2-chloro-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, cyclobutoxy, cyclobutyl, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropylmethoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy,2,3-difluorobenzyloxy, 3,5-difluorobenzyloxy, difluoromethoxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 2,3 -difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy,3-dimethylaminophenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 1,3-dioxolan-2-yl, 3-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylbenzyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, isobutoxy, isobutyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, 3-isopropylbenzyloxy, 3-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenxyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-telrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 2-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, 3-trifluoromethylthiobenzyloxy, and trifluoromethylthio; R₆ is selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl; R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl.
 12. The compound as recited in claim 11 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1: A is selected from the group consisting of 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl hexenyl, 1-ethyl--hexenyl, 1-pentyl-2-propenyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond; R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is hydrido, pentafluoroethyl, and trifluoromethyl; R₃ is selected from the group consisting of hydrido, methyl. trifluoromethyl, and difluoromethyl Y is a covalent single bond; Z is methylene; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₅, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy. cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy. 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaplithyloxy), trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy; R₆ is selected from the group consisting of fluoro and hydrido; R₇ is selected from the group consisting of hydrido and fluoro.
 13. The compound as recited in claim 11 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-4-hexenyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄ R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond; R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is hydrido, pentafluoroethyl, and trifluoromethyl; R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl Y is methylene; Z is a covalent single bond; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₅, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-( 1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy), trifluoromethoxy. 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl- 1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy; R₆ is selected from the group consisting of fluoro and hydrido; R₇ is selected from the group consisting of hydrido and fluoro.
 14. The compound as recited in claim 2 having the formula of:

or a pharmaceutically acceptable salt thereof, wherein; n is an integer selected from 1 through 2; A and Q are independently selected from the group consisting of —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H,

with the provisos that one of A and Q must be AQ-1H and that one of A and Q must be selected from the group consisting of AQ-2 and —CH₂(CR₃₇R₃₈)_(v)—(CR₃₃R₃₄)_(u)-T-(CR₃₅R₃₆)_(w)—H; T is selected from the group consisting of a single covalent bond, O, S, S(O), S(O)₂, C(R₃₃)═C(R₃₅), and C≡C; v is an integer selected from 0 through 1 with the proviso that v is 1 when any one of R₃₃, R₃₄, R₃₅, and R₃₆ is aryl or heteroaryl; u and w are integers independently selected from 0 through 6; A₁ is C(R₃₀); D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ is a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ is O, no more than one of D₁, D₂, J₁, J₂ and K₁ is S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ are N; B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C, C(R₃₀), N, O, S and a covalent bond with the provisos that no more than 5 of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are a covalent bond, no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are O, no more than two of B₁, B₂, D₃, D₄, J₃, J₄and K₂ are ,no more than two of B₁, B₂,D₃, D₄, J₃, J₄ and K₂ are simultaneously O and S, and no more than two of B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are N; B₁ and D₃, D₃ and J₃, J₃ and K₂, K₂ and J₄, J₄ and D₄, and D₄ and B₂ are independently selected to form an in-ring spacer pair wherein said spacer pair is selected from the group consisting of C(R₃₃)═C(R₃₅) and N═N with the provisos that AQ-2 must be a ring of at least five contiguous members, that no more than two of the group of said spacer pairs are simultaneously C(R₃₃)═C(R₃₅), and that no more than one of the group of said spacer pairs is N═N unless the other spacer pairs are other than C(R₃₃)═C(R₃₅), O, N, and S; R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl; R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl; R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl; Y is selected from the group consisting of a covalent single bond, (CH₂)_(q) wherein q is an integer selected from 1 through 2, and (CH₂)_(g)—O—(CH₂)_(k) wherein j and k are integers independently selected from 0 through 1: Z is selected from the group consisting of covalent single bond, (CH₂)_(q) wherein q is an integer selected from 1 through 2, and (CH₂)_(j)—O—CH₂)_(k) wherein i and k are integers independently selected from (0 through 1; R₃₀ is selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl with the proviso that R₃₀ is selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; R₃₀, when bonded to A₁, is taken together to form an intra-ring linear spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the point of bonding of a group selected from the group consisting of R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ wherein said intra-ring linear spacer is selected from the group consisting of a covalent single bond and a spacer moiety having from 1 through 6 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 10 contiguous members, a cycloalkenyl having from 5 through 10 contiguous members, and a heterocyclyl having from 5 through 10 contiguous members; R₃₀, when bonded to A₁, is taken together to form an intra-ring branched spacer connecting the A₁-carbon at the point of attachment of R₃₀ to the points of bonding of each member of any one of substituent pairs selected from the group consisting of subsitituent pairs R₁₀ and R₁₁, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₀ and R₁₂, R₁₁ and R₃₁, R₁₁ and R₃₂, R₁₁ and R₁₂, R₃₁ and R₃₂, R₃₁ and R₁₂, and R₃₂ and R₁₂ and wherein said intra-ring branched spacer is selected to form two rings selected from the group consisting of cycloalkyl having, from 3 through 10 contiguous members, cycloalkenyl having from 5 through 10 contiguous members, and heterocyclyl having from 5 through 10 contiguous members; R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylaimino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkiylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamiido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the provisos that R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen, that no more than three of the R₃₃ and R₃₄ substituents are simultaneously selected from other than the group consisting of of hydrido and halo, and that no more than three of the R₃₅ and R₃₆ substituents are simultaneously selected from other than the group consistubg, of hydrido and halo; R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are independently selected to be oxo with the provisos that B₁, B₂, D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C and S, no more than two of R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are simultaneously oxo, and that R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₃₁, and R₃₂ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen: R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₃₁, R₃₁ and R₃₂, R₃₂ and R₁₂, and R₁₂ and R₁₃ is used at the same time; R₉ and R₁₁, R₉ and R₁₂, R₉ and R₁₃, R₉ and R₃₁, R₉ and R₃₂, R₁₀ and R₁₂, R₁₀ and R₁₃, R₁₀ and R₃₁, R₁₀ and R₃₂, R₁₃ and R₁₂, R₁₁ and R₁₃, R₁₁ and R₃₂, R₁₂ and R₃₁, R₁₃ and R₃₁ and R₁₃ and R₃₂ are independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from 1 through 3 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, a saturated heterocyclyl having from 5 through 8 contiguous members and a partially saturated heterocyclyl having from 5 through 8 contiguous members with the provisos that no more than one of said group of spacer pairs is used at the same time; R₃₇ and R₃₈ are independently selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, hydroxy, amino, thio, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, cyano, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.
 15. The compound as recited in claim 14 having the formula of:

or a pharmaceutically acceptable salt thereof, wherein; n is an integer selected from 1 through 2; A is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, C3-C8 haloalkenyl, C3-C6 alkoxy C1-C2 alkyl, and C3-C8 hydroxyhaloalkyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ is a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ is O, no more than one of D₁, D₂, J₁, J₂ and K₁ is S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ are N; R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl; R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl; R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl; Y and Z are independently selected from the group consisting of a covalent single bond, oxy and alkylene; R₄ and R₈ are independently selected from the group consisting of hydrido and halo; R₅, R₆, and R₇ are independently selected from the group consisting of hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl; R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time; R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group group consisting of alkyl, halo, hydroxy, cyano, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl.
 16. The compound as recited in claim 15 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of ethyl, 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 2-octyl, 1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptynyl, 1-methyl-3-heptynyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptenyl, 1-methyl-3-heptynyl, 1-methyl-4-heptynyl, 1-methyl-5-heptynyl, 3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-4-hexenyl, 1-ethyl-2-hexynyl, 1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-propyl-2-pentynyl, 1-propyl-3-pentynyl, 1-butyl-2-butynyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, 3,3,3-trifluoropropyl, 2-methoxyethyl, 2-ethoxyethyl, 2-propoxyethyl, 2-isopropoxyethyl, 2-butoxyethyl, 2-isobutoxyethyl, 2-sec-butoxyethyl, 2-pentoxyethyl, 2-hexoxyethyl, 3-methoxypropyl, 2-methoxyisopropyl, 3-ethoxypropyl, 2-ethoxyisopropyl, 3-propoxypropyl, 2-propoxylsopropyl, 3-isopropoxypropyl, 2-isopropoxylsopropyl, 3-butoxypropyl, 2-butoxyisopropyl, 3-isobutoxypropyl, 2-isobutoxyisopropyl, 3-pentoxypropyl, and 2-pentoxyisopropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroarl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond: D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl, 1-indolizinyl, 7-indolizinyl, 1-isoquinolyl, and 2-quinolyl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R5, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆; R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, vinyl, phenyl, 4-trifluoromethylphenyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl; R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, ethyl, vinyl, trifluoromethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; Y and Z are independently selected from the group consisting of a covalent single bond, oxy, and methylene with the proviso that only one of Y and Z are simultaneously oxy; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₅, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of 4-aminophenoxy, benzoyl, benzyl, benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-bromo-2-nitrophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-butoxyphenoxy, chloro, 3-chlorobenzyl, 2-chlorophenoxy, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro-4-fluorobenzyl, 3-chloro-4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy. 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, cyclobutoxy, cyclobutyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl cyclopentylcarbonyl, cyclopropyl, cyclopropylmethoxy, cyclopropoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3.5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy 3,5-dimethylbenzyloxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, fluoro, 4-fluoro-3-methylbenzyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methylbenzoyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-trifluoromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, 3-iodobenzyloxy, isobutyl, isobutylamino, isobutoxy, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxycarbonylbutoxy, 3-methoxycarbonylprop-2-enyloxy, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, phenylsulfonyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy.tert-butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy. 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy. 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoroniethylthio; R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of cyano and hydroxy; R₆ is selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, trifluoromethyl, and trifluoromethoxy; R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl.
 17. The compound as recited in claim 16 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of ethyl, 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1 -methyl-5-hexenyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethylpentenyl, 1-butyl-2-propenyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 2-octyl, 1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methylthephenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptenyl, 3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-4-hexenyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl, 1-indolizinyl, 7-indolizinyl, 1-isoquinolyl, and 2-quinolyl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R₅, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆; R₁ is selected from the group consisting of trifluoromethyl. 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is selected from the group consisting of hydrido, methyl, ethyl, phenyl, 4-trifluoromethylphenyl, trifluoromethoxymethyl, 1,1,2,2-tetrafluoroethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl: R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl; Y and Z are independently selected from a covalent single bond and methylene; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₅, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy. 3-bromobenzyloxy. 4-bromophenoxy. 4-butoxyphenoxy, 3-chlorobenzyloxy, 2-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro4-methylphenoxy, 3-chloro-4-fluorophenioxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, cyclobutoxy, cyclobutyl, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl. cyclopropylmethoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy,2,3-difluorobenzyloxy, 3,5-difluorobenzyloxy, difluoromethoxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy,3-dimethylaminophenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 1,3-dioxolan-2-yl, 3-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylbenzyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 2-furyl, 3-furyl, heptafluioropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, isobutoxy, isobutyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, 3-isopropylbenzyloxy, 3-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenxyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy. 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 5-tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, 3-trifluoromethylthiobenzyloxy, and trifluoromethylthio; R₆ is selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl; R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl.
 18. The compound as recited in claim 17 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1: A is selected from the group consisting of 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-4-hexenyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅, and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 3-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R5, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆; R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is hydrido, pentafluoroethyl, and trifluoromethyl; R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl Y is a covalent single bond; Z is methylene; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₅, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy), trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy; R₆ is selected from the group consisting of fluoro and hydrido; R₇ is selected from the group consisting of hydrido and fluoro.
 19. The compound as recited in claim 17 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethylthexenyl, 1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl and 3,3,3-trifluoropropyl, wherein each member of group A may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of A to Z with one or more of the group consisting of R₃₃, R₃₄, R₃₅, and R₃₆ with the provisos that R₃₃, R₃₄, R₃₅ and R₃₆ must not be attached to the carbon directly linking A to Z and that R₃₃, R₃₄, R₃₅, and R₃₆ must be selected from other than aryl and heteroaryl when substituting the carbon 2 atoms from Z wherein Z is a single covalent bond; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, -5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 1,3,5triazin-2-yl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R5, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆; R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is hydrido, pentafluoroethyl, and trifluoromethyl; R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl Y is methylene; Z is a covalent single bond; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₅, R₃₃, R₃₄, R₃₅, and R₃₆ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropyiphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy. 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy), trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy; R₆ is selected from the group consisting of fluoro and hydrido; R₇ is selected from the group consisting of hydrido and fluoro.
 20. The compound as recited in claim 14 having the formula of:

or a pharmaceutically acceptable salt thereof, wherein, n is an integer selected from 1 through 2: A is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ is a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ is O, no more than one of D₁, D₂, J₁, J₂ and K₁ is S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ are N; R₁ is selected from the group consisting of haloalkyl and haloalkoxymethyl; R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl; R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl; Y and Z are independently selected from the group consisting of a covalent single bond, oxy and alkylene; R₄ and R₈ are independently selected from the group consisting of hydrido and halo; R₉ and R₁₃ are halo; R₅, R₆, and R₇ are independently selected from the group consisting of hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl; R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, is used at the same time; R₁₀, R₁₁, R₁₂, R₃₁, and R₃₂ are independently selected from the group group consisting of alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl; R₃₀ is selected from the group consisting of alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.
 21. The compound as recited in claim 20 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopent-2-enyl, cyclopent-3-enyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cyclohex-2-enyl, cyclohex-3-enyl, cycloheptyl, cyclohept-2-enyl, cyclohept-3-enyl, cyclooctyl, cyclooct-2-enyl, cyclooct-3-enyl, cyclooct-4-enyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 2H-2-pyranyl, 2H-3-pyranyl, 2H-4-pyranyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 2H-pyran-2-one-3-yl, 2H-pyran-2-one-4-yl, 2H-pyran-2-one-5-yl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3 -yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5yl, 1,2,4-triazin-6-yl, 1,2,3-triazin4-yl, 1-indolizinyl, 7-indolizinyl, 1-isoquinolyl, and 2-quinolyl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R5, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆; R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, vinyl, phenyl, 4-trifluoromethylphenyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl; R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, ethyl, vinyl, trifluoromethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; Y and Z are independently selected from the group consisting of a covalent single bond, oxy, and methylene with the proviso that only one of Y and Z are simultaneously oxy; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₉ and R₁₃ are fluoro; R₅, R₁₀ and R₁₂ are independently selected from the group consisting of 4-aminophenoxy, benzoyl, benzyl, benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy. 4-bromo-2-nitrophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-butoxyphenoxy, chloro, 3-chlorobenzyl, 2-chlorophenoxy, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro-4-fluorobenzyl, 3-chloro-4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, cyclobutoxy, cyclobutyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl cyclopropyl, cyclopropylmethoxy, cyclopropoxy 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyoxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, fluoro, 4-fluoro-3-methylbenzyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methylbenzoyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, -fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifuoromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, 3-iodobenzyloxy, isobutyl, isobutylamino, isobutoxy, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxycarbonylbutoxy, 3-methoxycarbonylprop-2-enyloxy, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, phenylsulfonyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy.tert -butoxy. 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethyl benzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoromethylthio; R₆, R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, trifluoromethyl, and trifluoromethoxy; R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl; R₃₀ is selected from the group consisting of chloro, ethoxy, ethyl, fluoro, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, isobutyl, isobutoxy, isopropoxy, isopropyl, isopropylthio, methyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, propoxy, propyl, sec-butyl, tert-butoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, trifluoromethoxy, and trifluoromethyl.
 22. The compound as recited in claim 21 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cycloheptyl, cyclooctyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2- dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbon may be optionally substituted with R₃₀, a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl, 1-indolizinyl, 7-indolizinyl, 1-isoquinolyl, and 2-quinolyl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R5, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆; R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is selected from the group consisting of hydrido, methyl, ethyl, phenyl, 4-trifluoromethylphenyl, trifluoromethoxymethyl, 1,1,2,2-tetrafluoroethoxymethyl, difluoromethyl, pentafluoroethyl, trifluoromethyl, and 2,2,3,3,3-pentafluoropropyl; R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl; Y and Z are independently selected from a covalent single bond and methylene; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₉ and R₁₃ are fluoro; R₅, R₁₀ and R₁₂ are independently selected from the group consisting of benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromophenoxy,4-butoxyphenoxy, 3-chlorobenzyloxy, 2-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, cyclobutoxy, cyclobutyl, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropylmethoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy,2,3-difluorobenzyloxy, 3,5-difluorobenzyloxy, difluoromethoxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy,3-dimethylaminophenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyioxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 1,3-dioxolan-2-yl, 3-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylbenzyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluorotrifluoromethylphenoxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, isobutoxy, isobutyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, 3-isopropylbenzyloxy, 3-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenxyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 2-oxazolyl, 4-oxazoyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl,tert -butoxy, 3-tert -butylphenoxy, 4-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5yl, thiophen-2-yl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluorometboxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, 3-trifluoromethylthiobenzyloxy, and trifluoromethylthio; R₆, R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl; R₇ is selected from the group consisting of hydrido, fluoro, and trifluoromethyl; R₃₀ is selected from the group consisting of chloro, ethyl, fluoro, heptafluoropropyl, 1,1,1,3,3.3-hexafluoropropyl, isobutyl, isopropyl, methyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, propyl, sec-butyl, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, trifluoromethoxy, and trifluoromethyl.
 23. The compound as recited in claim 22 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R5, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆; R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is hydrido, pentafluoroethyl, and trifluoromethyl; R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl Y is a covalent single bond; Z is methylene; R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₉ and R₁₃ are fluoro; R₅, R₁₀ and R₁₂ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy, 3-tert -butylphenoxy, 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy ),trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy; R₆, R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl; R₇ is selected from the group consisting of hydrido and fluoro.
 24. The compound as recited in claim 22 or a pharmaceutically acceptable salt thereof, wherein; n is the integer 1; A is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein a ring carbon other than the ring carbon at the point of attachment of A to Z may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉ position and two atoms from the point of attachment may be substituted with R₁₀, a ring carbon or nitrogen atom adjacent to the R₁₃ position and two atoms from the point of attachment may be substituted with R₁₂, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the R₁₂ position may be substituted with R₃₂, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R₁₁ and R₃₂ positions may be substituted with R₃₁; D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond to form the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 3-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a ring carbon atom adjacent to the carbon atom at the point of attachment may be optionally substituted with R₄ or R₈, a ring carbon atom adjacent to the R₄ position and two atoms from the point of attachment may be substituted with R5, a ring carbon atom adjacent to the R₈ position and two atoms from the point of attachment may be substituted with R₇, and a ring carbon atom three atoms from the point of attachment and adjacent to the R₅ and R₇ positions may be substituted with R₆; R₁ is selected from the group consisting of trifluoromethyl, chlorodifluoromethyl, and pentafluoroethyl; R₂ is hydrido, pentafluoroethyl, and trifluoromethyl; R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl Y is methylene; Z is a covalent single bond: R₄ and R₈ are independently selected from the group consisting of hydrido and fluoro; R₉ and R₁₃ are fluoro; R₅, R₁₀ and R₁₂ are independently selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, cyclopentyl, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 2-furyl, isobutyl, isopropoxy, 3-isopropylphenoxy, 3-methylphenoxy, pentafluoroethyl, 3-pentafluoroethylphenoxy 3-tert -butylphenoxy. 1,1,2,2-tetrafluoroethoxy, 3-(1,1,2,2-tetrafluoroethoxy )phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy),trifluoromethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, trifluoromethylthio, and 3-trifluoromethylthiophenoxy; R₆, R₁₁, R₃₁, and R₃₂ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl; R₇ is selected from the group consisting of hydrido and fluoro.
 25. A compound as recited in any one of claims 1 or 2, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of: 3-[[3-(4-chloro-3-ethylphenoxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-chloro-3-ethylphenoxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-chloro-3-ethylphenoxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-chloro-3-ethylphenoxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-chloro-3-ethylphenoxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-chloro-3-ethylphenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl] amino]- 1,1,1-trifluoro-2-propanol; 3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexylmethyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxyphenoxy)phenyl[(cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxyphenoxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-trifluoromethoxyphenoxy)phenyl](cyclopropylmethyl)amino]-1,1,1]-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxyphenoxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxyphenoxy)phenyl](3-pentafluoroethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3 -trifluoromethoxyphenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexylmethyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-isopropylphenoxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-isopropylphenoxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-isopropylphenoxy)phenyl](cyclopropylmethyi)amino]-1,1,1-trifluoro-2-propanol 3-[[3-(3-isopropylphenoxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-isopropylphenoxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-isopropylphenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-isopropylphenoxy)phenyl][3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexyl] methyl]amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(2,3-dichlorophenoxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(2,3-dichlorophenoxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(2,3-dichlorophenoxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(2,3-dichlorophenoxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(2,3-dichlorophenoxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl] amino]-1,1,1]-trifluoro-2-propanol; 3-[[3-(2,3-dichlorophenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(2,3-dichlorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexylmethyl] amino]1,1,1-trifluoro-2-propanol; 3-[[3-(4-fluorophenoxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-fluorophenoxy)phenyl](cyclopentylmethyl)amino-1,1,1-trifluoro-2-propanol; 3-[[3-(4-fluorophenoxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-fluorophenoxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-fluorophenoxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(4-fluorophenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol, 3-[[3-(4-fluorophenoxy)phenyl][3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexylmethyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxybenzyloxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxybenzyloxy)phenyl](cyclopentylmethyl )amino]-1,1,1-trifluoro-2-propanol; 3-[[3 3-trifluoromethoxybenzyloxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxybenzyloxy)phenyl](3-trifluoromethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxybenzyloxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxybenzyloxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethoxybenzyloxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-cyclohexylmethyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethylbenzyloxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethylbenzyloxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethylbenzyloxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethylbenzyloxy)phenyl][(3-trifluoromethyl)cyclohexyl -methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethylbenzyloxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethylbenzyloxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[3-(3-trifluoromethylbenzyloxy)phenyl][3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexylmethyl] amino]-1,1,1-trifluoro-2-propanol, 3-[[[(3-trifluoromethyl)phenyl]methyl](cyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl](cyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl](cyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](cyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethyl)phenyl]methyl](4-methylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl](4-methylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenylmethyl](4-methylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl(4-methylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethyl)phenyl]methyl](3-trifluoromethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl](3-trifluoromethylcycloohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl](3-trifluoromethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3-trifluoromethylcyclo-hexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)cyclo-hexyl]amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)cyclo-hexyl] amino]-1,1,1 -trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)cyclo-hexyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-cyclohexyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethyl)phenyl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-4-fluoromethyl)phenyl]methyl](3-isopropoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl](3-isopropoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl](3-isopropoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3-isopropoxycyclohexyl)-amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethyl)phenyl]methyl](3-cyclopentyloxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl](3-cyclopentyloxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl](3-cyclopentyloxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3-cyclopentyloxycyclohexyl)-amino]-1,1,1-trifluoro-2-propanol; 3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl)(3-isopropoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl](3-cyclopentyloxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(2-trifluoromethyl)pyrid-6yl]methyl](3-trifluoromethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(2-trifluoromethyl)pyrid6-yl]methyl][3-(4-chloro-3-ethylphenoxy)cyclo-hexyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl][3-(1,2-tetrafluoroethoxy)cyclo-hexyl] amino]-1,1,1 -trifluoro-2-propanol; 3-[[[(2-trifluoromethyl)pyrid-6yl]methyl](3-pentafluoroethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol; 3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl](3-trifluoromethoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol 3-[[[(3-trifluoromethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)propyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)propyl]-amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)propyl]-amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1 2,2-tetrafluoroethoxy)phenyl]methyl](3-(4-chloro-3-ethylphenoxy)-propyl]amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-2,2,-di-fluroropropyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-2,2,-di-fluroropropyl] amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-2,2-di-fluroropropyl]amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-2,2,-difluroropropyl]amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethyl)phenyl]methyl][3-(isopropoxy)propyl]amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-pentafluoroethyl)phenyl]methyl][3-(isopropoxy)propyl]amino]-1,1,1-trifluoro-2-propanol; 3-[[[(3-trifluoromethoxy)phenyl]methyl][3-(isopropoxy)propyl]amino]-1,1,1-trifluoro-2-propanol; 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-(isopropoxy)propyl] amino]-1,1,1-trifluoro-2-propanol; and 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-(phenoxy)propyl] amino]-1,1,1-trifluoro-2-propanol.
 26. A pharmaceutical composition comprising a compound of one of claims 1 through 25 together with a pharmaceutically acceptable carrier.
 27. A method of treating coronary artery disease or other CETP-mediated disorders in a subject by administering a therapeutically effective amount of a compound of one of claims 1 through
 25. 28. A method of preventing coronary artery disease or other CETP-mediated disorders in a subject by administering a therapeutically effective amount of a compound of one of claims 1 through
 25. 29. A method of treating or preventing cerebral vascular accident (CVA) or other CETP-mediated disorders in a subject by administering a therapeutically effective amount of a compound of one of claims 1 through
 25. 30. A method of treating or preventing dyslipidemia and other CETP-mediated disorders in a subject by administering a therapeutically effective amount of a compound of one of claims 1 through
 25. 